8Information for users of Titration and pH Systems, Density Meters and Refractometers

Contents

Basics

• Dip rinsing – more efficient than you think! 2

• Practical implementation of LabX in an evolving Part 11 environment 5

Expert tips

• The most frequent causes of error when measuring the density and refractive index of liquids 10

• Seven tips for LabX users 13

Applications

• Control of "purified water" and "water for injection" to USP requirements 15

• Fully automatic COD determination with the Rondo60 18

New products

• New products 22– Densito 30PX, Refracto 30PX– Refracto 30GS– SevenEasy 23– SevenMulti– InLab®425

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C. Gordon

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Dip rinsing – more efficient than you think!

When developing and validating a titration method, it is not only the titration itself that has to be checked, but also the entire analysis including sample preparation and cleaning of the sensor, stirrer and burette tip between samples. The question often arises as to how effective does the rinsing have to be to prevent carryover. The following article gives some details of the effectiveness of simply dipping the titration head in a cleaning solution between samples.

The standard configuration of the METTLER TOLEDO Rondolino au-tomatic titration stand does not in-clude a rinse head and pump but relies simply on dipping the titra-tion inserts (sensor, stirrer, burette tip) in a beaker of clean solvent be-tween samples. To investigate the ef-fectiveness of this method of clean-ing, three different applications were used. The first was chosen as a typi-cal application of titration while the other two were selected because they are usually very sensitive to carry-over.

Example 1: Dip rinsing in acid-base titrationsFor the titration of 5 mL of 0.1 M HCl with 0.1 M NaOH, a series of 9 samples was titrated with a 10 s dip rinse between samples using a dy-namic equivalence point titration to a first equivalence point. Termi-nation at the first equivalence point is critical so that there is not a large excess of base carried to the clean-ing beaker containing deionized water and to the next sample. Of interest in this test was whether the first sample differed from the other

samples (titration head clean be-fore the first sample) and whether there was a decreasing or increas-ing trend in the results. The results (Fig. 1) show that neither of the above is the case. In addition to the above, a comparison was made with an identical series, this time with a 10 mL rinse between samples using a diaphragm pump and the Power-Shower® rinse head (Fig. 2). This comparison showed no significant differences in either the mean re-sult (0.1004 mol/L) or the precision (%RSD = 0.083%).Fig. 1: Acid/base titration with 10 s dip rinsing

Fig. 2: Acid/base titration with PowerShower® rinsing

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Example 2: Dip rinsing in direct ion concentration determinationThe second analysis chosen to test the effectiveness of the so-called

“dip rinse” was that of direct mea-surement of fluoride ion content us-ing an ion-selective electrode (ISE). For this test 3 sample solutions were prepared containing approximately 10, 100 and 1000 ppm fluoride re-spectively. These samples were then arranged in an alternating fashion i.e. 10, 100, 1000 repeated 3 times to give a total of 9 samples. With sig-nificant carryover one would then expect an increase in the 10 ppm re-sults over the series and a decrease in the 1000 ppm results. The results here show that there is some carry-over although fairly small with the 10 ppm sample ranging from 10.0 to 10.3 (Fig. 3) and the 1000 ppm sam-ple ranging from 1025.8 to 1022.5 (Fig. 4). The 100 ppm sample re-mained almost unchanged.

Although this test seems to indicate that the rinsing is not very effective, one should take into account that an increase from 10.0 to 10.3 ppm is due to a decrease in measured

signal from pX = -1.000 to -1.015 or a change in mV signal of only 0.9 mV. In the case of the 1000 ppm sample, this change is only from pX = -3.011 to -3.010.

Example 3: Dip rinsing in titrations with large pH difference between beginning and endThe last test, and one of the most sensitive to poor cleaning, was the titration of the total alkalinity of a sample with low buffer capacity, in this case, tap water. Because of the low endpoint in the titration of pH 4.3, any carryover to the next sample would be expected to have a signifi-

cant effect on the initial pH of the sample. Figure 6 shows the initial pH of the samples over a series of 5 and indicates very little effect over the series (from pH 7.826 to 7.790). In addition, the total alkalinity re-sult is virtually unaffected (Fig. 7).

ConclusionWhen does one need to rinse using a pump? Clearly, with dirty samples that tend to stick to the titration head inserts, it is always advisable to use an effective rinse. In addition it Fig. 3: 10 ppm fluoride sample with dip rinsing

Fig. 4: 1000 ppm fluoride sample with dip rinsing

Fig. 5: METTLER TOLEDO Rondolino during dip rinsing

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Fig. 6: Initial pH with dip rinsing

Fig. 7: Total alkalinity with dip rinsing

is also recommended in the follow-ing cases:

• In any analysis where the titration is not terminated after the equivalence point but continues to some other termination criteria (potential, slope, and/or maximum volume).

• For the direct measurement of ions in samples of widely varying concentrations.

• For samples where a pH buffer is added and the initial sample

pH prior to the buffer addition is measured and of importance.

• For any analysis where a blank correction has to be made due to solvent effects.

• In general, any analysis where the highest accuracy and precision are required.

Although effective rinsing with a clean solvent is always the best course of action, the above tests show that in many cases simple dip rinsing is sufficient.

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T. Butta

B a s i c s B a s i c s

Practical implementation of LabX in an evolving Part 11 environment

With the latest draft guidance document on 21 CFR Part 11 just released by the U.S. FDA, what are the practical steps that, when implementing a LabX solution, can assist user organizations with compliance given the evolving interpretation of the regulation?

21 CFR Part 11 – A moving targetIn UserCom 7, our subject matter experts provided an overview of the U.S. Food and Drug Administration’s (FDA) 21 CFR Part 11 regulation governing the use of electronic re-cords and electronic signatures, as well as the advantages of employing networked instrument control and data acquisition software such as METTLER TOLEDO LabX pro. [1]

Since the Part 11 regulation went into effect in August of 1997, the FDA has released periodic Guidance Documents intended to elucidate its current thinking on the subject and to provide guidance to industry on compliance with the regulation. Since our publication of UserCom 7, the most recent draft guidance document on Part 11 was released Feb. 20, 2003 by the FDA. This has been done as part

of a current revision underway to the GMPs (Good Manufacturing Practices) toward more risk-based assessment of system criticality as a determinant of validation effort. The new draft guidance document recommends that organizations should perform an assessment of prospective automated systems to determine the degree to which faults in such systems pose a potential risk to public health, and are thereby subject to Part 11 as a result of their application within the organization.

With the evolving nature of the regulation, the prudent organization will limit its potential exposure. By implementing quality management processes to insure compliance with Part 11 wherever automated systems operate within the scope of the predicate rules (those issued prior to Part 11 which govern the management of records, personnel activities, training, etc.), organizations will certainly benefit by avoiding potential problems wherever the integrity of critical data from these systems could be called into question.

Part 11, LabX, and applicabilityLabX pro for titration automation has been in general release since late 2001 with hundreds of user li-censes now active in both regulated and non-regulated industries. LabX is becoming the connective platform for many METTLER TOLEDO manu-factured instruments in the labora-tory or plant with future LabX mod-ules for balances, pH meters, density meters, and more scheduled on the product calendar. This offers the prospective client organization a re-duction in the total number of indi-vidual systems needed to automate its instruments, and a reduction in Validation logbooks facilitate planning and execution

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Fig. 2: LabX with titrator in daily use

the overall costs of initial installa-tion, validation, training, and ongo-ing maintenance, and in the man-agement of its data.

LabX pro has been designed for use where high standards of quality control are employed – such as in regulated industries like pharma-ceutical development and produc-tion, medical device manufacturing, and environmental monitoring and where work is performed accord-ing to Good Laboratory Practices, Good Manufacturing Practices, etc. (collectively “GxP”). As such, LabX is typically involved in an area of work within the regulated organiza-tion that would cause it to fall under Part 11.

For users of LabX and other instru-ment control and e-data collection systems, compliance should be made easy and cost-effective with well-de-fined regulatory assistance programs and other service options from in-strument suppliers. Following, we describe the general phases involved in implementing the METTLER TO-LEDO LabX pro solution in a GxP en-

vironment where 21 CFR Part 11 ap-plies, and describe the requirements and options available at each stage of the process.

Steps to implementing LabX in a regulated environmentLabX pro is easily deployed in a stand-alone or medium-sized networked workgroup, and ready for produc-tive use in regulated environments within a short timeframe. The LabX implementation process in a Part 11 environment consists of a few logical steps. For a stand-alone workstation installation, the steps will be shorter and somewhat less intensive versus a large networked deployment. In gen-eral, from project initiation to go-live, implementation in a medium sized laboratory installation can take place in as few as 45 days.

1. Vision / ScopeDuring this initial phase, depart-mental and/or organizational ob-jectives for an automated titration system are considered. As part of the exploratory process of the LabX ap-plication, representatives from the organization‘s end-user, lab man-agement, validation, IT, regulatory compliance department, and possi-bly outside consultants will typically meet with METTLER TOLEDO rep-resentatives to discuss and evaluate the LabX feature set in-depth, and to review vendor support programs available to the organization. Sys-tem functionality is reviewed and demonstrated, support for Part 11 assessed, and discussions regard-ing the degree of fit to the organi-zation‘s preliminary objectives are considered. Pending completion and

a decision to move forward, a deter-mination of project scope and a high level cost / benefit analysis can be performed. A determination of the number of instruments to be con-nected, and the number of comput-er workstations is made. Review and concurrence on final project scope between customer and supplier fol-lows before the next stage.

2. Supplier AuditConfigurable software systems such as LabX are classified “Category 4 software” according to the GAMP 4 [2] guide – the generally accept-ed industry reference guide for the validation of automated systems. For Category 4 software, an orga-nization is required to carry out an audit of suppliers from which it acquires software used for certain research & development and pro-duction functions. The intent is to determine and document the qual-ity standards employed by the sup-plier during the development phase (Specification Qualification and Construction Qualification) as is re-quired by GMP standards. To assist with this requirement, METTLER TOLEDO has produced Volume I of the LabX Validation Manual. The manual provides a detailed overview of the quality standards applied dur-ing the life cycle development phase of the LabX application. Use of the manual allows the customer orga-nization to save time and expense by performing a “remote” audit of METTLER TOLEDO. Any gap in the audit requirements of the customer organization is subsequently ad-dressed by METTLER TOLEDO in a timely fashion.

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Fig. 3: All relevant changes are documented in the audit trail

3. Implementation and validation planningFollowing, or concurrent with the Supplier Audit, the overall validation plan is developed by the user organi-zation. The purpose of the plan is to match each the design, functional, and user specifications with specific test protocols that will provide docu-mented evidence that the system will routinely produce results consistent with the original specifications. To assist with this planning, Volume II of the LabX Validation Manual is available to the customer organiza-tion and contains templates, guide-lines, and step-by-step procedures for all phases of the validation pro-cess such as System Requirements (SR), Installation Qualification (IQ), and Operational Qualification (OQ) of the LabX system. Along with use of the Volume I discussed previ-ously, a traceability matrix is easily developed matching all functional and user requirements specifica-tions with the design, and linked to specific test protocols that are con-tained in Volume II, or to additional protocols that will be developed by the user organization.

Services to be performed by METTLER TOLEDO such as the IQ and OQ on connected instruments and on the LabX system per the protocols contained in Volume II are incorporated into the overall plan. A task-based project team is formed. A typical team for a LabX implementation is from one to five people, usually dictated by the total number of end users, and the size of the installation (i.e. stand-alone, work group, or enterprise-wide). System design objectives are devel-oped during this step; that is - the planning, building, and testing of

the computing hardware that will host the connected instruments. Existing computing hardware is selected to run the application, and/or new hardware is installed and co-existence strategies with previously installed applications are determined. If LabX will be de-ployed in networked configuration, Ethernet networking is installed and user accounts are set up at the operating system level. The organization’s user policies are re-viewed and a subsequent configu-ration plan for instrument con-nections is developed in order to maximize user access and instru-ment availability on the system consistent with the policies. An education/training strategy is de-termined. Will group vendor train-ing be provided, or will a train-the-trainer approach be taken? This stage is concluded with a meeting to discuss and review responsibili-ties for the next steps.

4. Device Installations and associated Equipment Qualifications (EQ)Independent of the LabX system, ti-trators, balances, pH meters, etc., like most laboratory instruments in a regulated environment, must be qualified in order to provide docu-mented evidence that they are in accord with the manufacturer’s in-stallation and operational specifica-tions. While an organization may develop its own equipment qualifi-cation (EQ) process, most will look to the supplier for assistance with appropriate test procedures, and in order to save time and effort.For each titrator series manufactured by METTLER TOLEDO, EQ protocols are contained in individual instrument logbooks documenting the specific IQ and OQ procedures delivered by trained and certified METTLER TOLEDO field engineers. The protocols are consistent on a worldwide basis – useful to multi-

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Fig. 4: LabX documentation

Fig. 5: LabX data entry form

national companies that may wish to perform a technology transfer of a LabX system at a subsequent date. The work procedures are filed as part of the METTLER TOLEDO quality management system, and involve specific metrological devices used to test and certify the titrator sensor inputs, amplifier, and titrant delivery system. The EQ service provides certified reagents and primary test standards for performance of a general system suitability test. Balances, density meters, refractometers, and pH meters are also qualified using their own individual logbooks. The EQs are designed as stand-alone protocols, but are also intended to form the foundation test layer of a LabX implementation, proving that instruments meet all specifications prior to their incorporation into an automated system. Calibration certificates are subsequently issued and included in the appropriate section of the logbook setting the stage for the next step.

5. LabX deployment and validation testingUsing custom developed test proto-cols, or those contained in Volume II of the LabX Validation Manual, the

customer organization’s validation specialist or designated third-par-ty begins the software installation and validation process. If elected, a METTLER TOLEDO Software Vali-dation Engineer is engaged to as-sist the organization in performing the validation. The system is vali-dated prospectively, meaning that the validation process takes place in conjunction with the project life cycle. At each stage of the software development process, METTLER TOLEDO conducts system and unit testing to insure adherence to the original design specifications and to insure quality standards. The soft-ware is delivered with a Declaration of System Validation. As a result, the user organization is not required to retrospectively validate the applica-tion. In simple terms, this means that the user does not need to vali-date the accuracy of mathematical calculations, the integrity of coding logic, and the like. Rather, the focus is on the operational aspects of the system such as communication with the connected instrument(s), and the proper routing and backing up of data within the network.When a METTLER TOLEDO validation engineer is employed, the LabX system files are next loaded and verified according to the IQ, and validation testing ensues following the established protocols per the OQ defined in Volume II of the LabX Validation Manual and is documented by the engineer. The completed templates in Volume II remain as a permanent record of the validation testing process.

The validation engineer works with the user organization to perform the

work that comprises the elements of the validation including the following: identification of all user Standard Operating Procedures, identification of all computing and instrument hardware components, documentation and testing of the network environment, data acquisition, access mechanisms, user administration functions, audit trail, system security, and backup procedures, among others.

6. Device and software end-user trainingAt this stage, end users may be trained on the instruments and the software application. It is impor-tant not to overlook this important step, as the benefits that will accrue from use of the system are propor-tional to the level of training effort. Good Laboratory Practices require that analysts are trained according to procedures or protocols that suf-ficiently give the analysts the knowl-edge to use the equipment, and is re-quired by both GLP and GMP, as well as specified within the Part 11 regu-lation itself.

Consideration of the end users’ prior experience with the instrument(s), if any, is accounted for in the train-ing strategy, and a customized or

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standardized curricula can be de-livered in a group format or on an ad hoc basis on-site by qualified METTLER TOLEDO professionals on all aspects of the system includ-ing instruments, LabX end user, and system administration functions. A comprehensive training covering all aspects of the system can range from 1 to 4 days and can include workshops.

7. Perform remaining validation actions and finalize validation reportAfter completion of the deployment, validation, and training phases, a meeting is conducted to review re-maining items and document any deviations from the original vali-dation plan. Any remaining Per-formance Qualifications (PQs) not conducted as part of the earlier validation phase are conducted primarily by the customer organi-zation to provide documented evi-dence that expected results were obtained over the entire intended operational range of the system us-ing actual validated methods. The final validation report is completed and issued and a strategy for fu-ture change control is established. To assist in maintaining a vali-dated state, updates and new ver-sions of LabX are delivered by MET-TLER TOLEDO with templates for the minimum level of re-valida-tion that should be undertaken, the completed versions of which can be placed into Volume II of the valida-tion manual. A review of organiza-tional procedures for making physi-cal changes to the system, such as the addition of a new workstation or instrument, is outlined.

8. System go-live and post-implementation reviewThis is the final phase for the entire project. During this phase, manage-ment approval for live use of the sys-tem is obtained and users go-live on the LabX system. Close moni-toring during the early live use of the system should be conducted to help ensure a seamless transfer from manual procedures. Software maintenance agreements and sup-port procedures are reviewed at this time.

A post-implementation review meeting is subsequently conducted among all participants during which a review of the project is conducted, and lessons learned are documented to provide a foundation for future projects.

SummaryUnlike more complex systems such as those for chromatography and Laboratory Information Manage-ment Systems (LIMS), METTLER TOLEDO LabX is easily installed and ready for use in a regulated environ-ment with relatively less effort. The benefits of automating instrument control and electronic acquisition and archiving of data and - in the near future, collection of weight measurements and other METTLER TOLEDO instrument data, is facili-tated with supporting vendor pro-grams, services, and consultation at each stage. The Part 11 regulation is likely to undergo further revision and clarification, but organizations can take advantage of the benefits of automated systems such as LabX today despite the uncertainty, by following a structured approach to

implementation and validation that take into account quality manage-ment processes and generally ac-cepted industry guidelines.

NoteIn the United States, the domestic market of the author, Tom Butta, METTLER TOLEDO offers a compre-hensive support, as described in this text. This is also the case in many other countries. Nevertheless the ex-tent of the service can differ from country to country. Please enquire at your local METTLER TOLEDO market organization as to the ex-tend of the service available in your country.

Footnotes:[1] Gordon C. UserCom 7

ME-51710185 published by Met-tler-Toledo GmbH, 8, 11(05/2002)

[2] GAMP 4 is copyright ISPE 2001

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P. Wyss

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RE40D refractometer with SC1 sample delivery and cleaning unit

The most frequent causes of error when measuring the density and refractive index of liquids

Modern digital instruments are easy to use and allow the density and refractive index of liquids to be determined with a high degree of accuracy. High-resolution instruments are however no guarantee for accurate results. This article explains what precautions should be taken to avoid errors when measuring the density and refractive index of liquids.

Density measurements with a pyc-nometer are not so easy to perform. Even if suitable equipment is avail-able, much time, skill and experi-ence are required to achieve an ab-solute accuracy of 1 · 10-5 g/cm-3

with this method. This seems to be much easier with modern digi-tal density instruments: just inject the sample, press the button, and the density value appears on the display with a resolution of up to

five decimal places. At first sight, one might think that experience and skill are unnecessary for such measurements. However, a number of important requirements must be fulfilled if the density values shown on the instrument display are to be correct:

• The absolute accuracy of the in-strument must be ensured (cor-rect adjustment).

• The measuring cell must con-tain only the sample to be mea-sured during the measurement.

• The nature of the sample must be such that an accurate mea-surement is possible.

The information given below will help you to fulfill these prerequi-sites and thereby largely eliminate measurement errors when perform-ing density and refractive index measurements with digital instru-ments.

InstrumentThe commonly held opinion that frequent adjustment of the instru-ment guarantees accurate results is a somewhat mistaken belief. Any adjustment operation results in changes being made to internal instrument settings. If the adjust-ment is not properly performed, all the measurements performed af-terward are wrong! Instead of frequent adjustment, it is in fact better to regularly check the mea-surement accuracy of the system by measuring a sample of accu-rately known density or refrac-tive index (e.g. distilled water or a standard). If the value obtained deviates from the expected (true) value, the measuring cell must be thoroughly cleaned and the same sample measured again. The in-strument should only be adjusted if the result of the second mea-surement is also wrong.The “Check” function allows the measurement accuracy of the METTLER TOLEDO DE density me-ters, RE refractometers and DR45 combined meter to be easily verified. This function also ensures that such instrument tests are performed at regular intervals.The main reasons for improper ad-justment are as follows:

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Warning message of the automatic error detection

Density meters(1) The measuring cell has depos-its of previously measured products. Such deposits are not always visible. For example, if products containing oil or fat are measured, the measur-ing cell may be coated with a very thin film of oil. To prevent this, the cell should be cleaned with a suit-able rinsing solution - preferably af-ter each measurement. It is in fact very easy to determine whether resi-dues of oil or fat have been deposit-ed. All you have to do is to measure the density of air (dry the cell thor-oughly beforehand) and of distilled water: if the density value displayed for air is too high and that for dis-tilled water too low, the measuring cell is very likely coated with an oil film. In this case, the cell must be thoroughly cleaned using a suitable solvent and the test repeated. This allows you to decide whether or not an adjustment of the instrument is really necessary.

(2) The measuring cell is not per-fectly dry when adjustment in air is performed. To ensure dryness, the cell should be rinsed with a volatile solvent (e.g. acetone) and then dried by passing dry air through it for at least three minutes before perform-ing an adjustment.

Refractometers(3) The surface of the prism may be contaminated with an invisible de-posit of previously measured prod-ucts. For this reason, the surface of the prism must be thoroughly cleaned before performing an ad-justment.

Density meters and refrac-tometers(4) The temperature of the measur-ing cell is not stable when the adjust-

ment is performed. If possible, never switch off instruments with built-in Peltier thermostats. If the instru-ment is switched off, wait at least one hour after switching on again before performing an adjustment.

Check the measurement accuracy of the system after each adjustment by measuring a sample of accurate-ly known density or refractive index (e.g. distilled water). Repeat the ad-justment if the measured value is wrong. This procedure enables im-proper adjustments to be largely eliminated.

Measuring cellDensity meters(5) Air bubbles in the measuring cell are one of the most frequent causes of measurement errors in density determinations. Air bubbles may be introduced together with the sample into the measuring cell, or may form during the measurement as a result of the sample degassing.In particular, be careful when mea-suring viscous samples and make sure that the samples do not con-tain air bubbles when you introduce them into the measuring cell. It of-ten helps to warm the sample in a closed vessel and to allow it to stand for a few minutes before the mea-surement. The viscosity of the sam-ple decreases on warming and air bubbles can more easily escape.The solubility of a gas in a liquid usually decreases with increasing temperature. For this reason, samples that show a tendency to degas should be warmed to a temperature above that of the measurement before introduction into the measuring cell. Further-more, the samples should always be introduced into the measuring cell under positive pressure and not, as

is usually the case with many auto-mated sampling pumps, sucked into the cell (risk of degassing due to re-duced pressure).

Refractometer(6) If the temperature of the mea-suring cell is below that of the sur-roundings, a film of condensed moisture may form on the measur-ing cell and on the surface of the prism. Make sure that the measur-ing cell is completely dry before in-troducing the sample.

Density meters and Refrac-tometers(7) Make sure that the measuring cell does not contain any residues of rinsing solutions or previously mea-sured samples. Clean and dry the measuring cell thoroughly before each measurement or rinse it with a larger volume of the next sample to

be measured. Note: Rinsing with the next sample of course only makes sense if the sample is in fact able to dissolve the residues in the measur-ing cell!Please remember that residues of previously measured samples in the measuring cell are not always visible (see point 1).

SampleDensity instruments(8) The shear forces that arise when viscous samples are measured in the measuring cell can lead to inaccu-

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Source of error (1) (2) (3) (4) (5) (6) (7) (8) (9) (10) (11) (12) (13)

with SC1 / SC30 – –

rate results. The value of the den-sity displayed by the meter is then usually too high [1]. All METTLER TOLEDO DE density meters are able to automatically correct the sample viscosity measurement error. If your density meter has such viscosity cor-rection, you should always switch it on if you want to obtain the best pos-sible accuracy with samples whose viscosity is > 25 mPa·s.

Refractometers(9) The stray light that arises when turbid samples are measured (sus-pensions and emulsions) can lead to erroneous results. To estimate the measurement error due to stray light, you should measure your sam-ples again after filtering and then compare the results obtained from the filtered and unfiltered samples. In addition, you should stir such samples with a plastic rod after in-troduction into the measuring cell before performing the measurement.

(10) If volatile samples are measured, part of the sample can evaporate dur-ing the actual measurement. The energy needed for the evaporation process cools the prism. This can

interfere with the temperature con-trol of the measuring cell and pre-vent accurate thermostating of the sample. For this reason, when you measure volatile samples, you should either perform the measurement at a low temperature (point 6), or seal the measuring cell with a lid.

Density meters and refrac-tometers(11) If highly concentrated sam-ples are cooled in the measuring cell (sample temperature → mea-surement temperature), part of the sample may crystallize out before or during the measurement. This can lead to large measurement er-rors. Make sure that the sample does not crystallize out on cooling to the measurement temperature, or work at a higher measurement tem-perature.

(12) If solutions or suspensions are allowed to stand for a longer period of time, part of the solid material may settle or a concentration gradi-ent may be formed. Stir the sample well before taking a sample. Make sure that no air bubbles are formed during stirring. If you have to mea-

sure suspensions, it is often not pos-sible to completely homogenize the sample. In such cases, you should repeat the measurement several times and calculate the mean value of the individual measurements in order to obtain reliable values.

(13) Make sure that the sample does not undergo change before the mea-surement is performed. Store the samples in a tightly sealed vessel up until measurement.

If samples are transferred manu-ally into the measuring cell for density and refractive index de-terminations, it is the operator’s responsibility to take the possible causes of errors described here into account. Measurement errors can thus never be completely excluded.

When the SC1 and SC30 sample de-livery and cleaning units are used, the METTLER TOLEDO DE density meters, the RE refractometers and the DR45 combined meter are able to exclude most sources of error, or automatically detect them, warn the user and mark the result as inaccu-rate (see table).

Error can be largely excluded. Error is automatically detected and the result marked as inaccurate. Error is detected in most cases and the result marked as inaccurate. Reliable measurement values thanks to automatic repeat measurements.

[1] Influence of sample viscosity on density measurements with the oscillating tube technique, UserCom 6, 06.2001.

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Ch. Bircher

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Fig. 1: Screenshot

*Tips marked with an asterisk are only available for LabX professional

Seven tips for LabX users

There are a number of interesting possibilities that probably not every user is aware of lying dormant beneath the simple, elegant surface of the LabX titration software. The following article reveals seven practical tips for everyday use.

Everyone his own LabX!*Do you work in shifts? Or do several persons use the same PC? If so, LabX is ideal for this kind of operation. The program can be opened several times – actually in theory as many times as you like, until the computer runs out of memory. A new user can log on each time the program is opened. This means, for example, that the lab manager can quickly change a method while a lab assistant is running a series of 20 samples on the same PC – even if the lab assistant is not allowed to access the method editor. And, of course, it goes without saying that everything is properly recorded in the audit trail under the persons concerned.

Clone titrators?LabX has an instrument backup function. As the name suggests, its primary purpose is to secure all the settings of a titrator.If you have several instruments, this feature provides you with an additional application possibility: you can copy each backup to other titrators of the same type. This allows you to rapidly create identical copies of a titrator. In this way, all the titrators in a laboratory can easily be set to the same level.A backup can also be sent by e-mail to another laboratory. This allows standardization of all the instruments in the plant to be achieved in the simplest possible way.If you do not want to clone all the instrument settings, but just part of the individual data, such as the sensor database, this can also easily be done: just save the data from the reference instrument and then copy it to other instruments.The details on how you do this are explained in the LabX operating instructions.

Copy whatever you wantAll the different graphics in LabX, such as titration curves and control charts, can be copied to Microsoft Word or to other (word-processing) programs: simply click the desired chart, choose the “Copy” com-mand in the “Edit” menu (or press Ctrl+C), change to Microsoft Word, and choose “Paste” in the “Edit” menu. In Word, you can scale and edit the chart as much as desired.But that’s by no means all. In just the same way, you can copy prac-tically all the tables and texts in LabX to other application pro-grams. For example, you can select the relevant part of a method in the method editor, copy it with Ctrl+C and then insert it with Ctrl+V into another program such as Microsoft Word.

Starting the Audit Trail program directly from LabX*Anyone who works in an FDA-regu-lated environment must sometimes be able to access the audit trail, the LabX “logbook”. Since the audit trail viewer is in fact a separate program, it also has to be started in addition to LabX. There is however a way to start the Audit Trail program direct-ly from LabX:

1. In the “Tools” menu, choose the “Customize” command.

2. A dialog box appears. Click the “Add” button.

3. In the “Menu entry” box, enter the name “Audit Trail” (or what-ever you like).

4. Press the button with the three points in the “Command” box.

14 15

E x p e r t t i p s A p p l i c a t i o n s

Fig. 2: Screenshot

*Tips marked with an asterisk are only available for LabX professional

5. A file selection box appears. Look for the AuditTrail.exe file on your hard disk. It can usually be found under C:\Programme\Mettler-To-ledo GmbH\AuditTrail\. Select the file and press the “OK” but-ton. The dialog box should now be similar to that shown in Fig. 1 (screen shot). Now close the dialog box by clicking the “OK” button.

6. Select the “Tools” menu again. It now includes the Audit Trail com-mand. If you choose it, the Audit Trail is started.

You can use the same procedure described above to start any other program from LabX.

Directly into the networkIs your titrator too far away to connect to LabX on a computer via the standard serial connection? For example, the instrument is in a production facility?There’s a simple solution: any LabX-compatible titrator can be linked di-rectly to an existing Ethernet net-work via the METTLER TOLEDO e-link Box. You do this by connect-ing the titrator to the e-link Box with a serial cable and then connecting the Box to the network just like a computer.

Computer switched off– titration continues*With LabX so-called instrument servers can be set up. An instrument server is a normal PC whose only purpose is to control titrators. LabX is installed on the instrument server (to be more precise, the LabX instrument server component); the software is however operated from other computers, typically the workstation computers of the different users.At first sight, this may appear complicated. It does, however, have several important advantages: for

example you can log on or log off at the workstation computer even if a titration is running. You can even simply switch off any workstation computer – the titrations remain unaffected. If you start a workstation computer again afterward, you can continue to follow the titration you previously started! You just have to make sure that the instrument server does not get switched off.The installation of such as system is relatively easy. Our product specialists will be pleased to advise you.

Rapid and easy filteringFinally a tip for more experienced LabX users: From Version 1.1 on-ward, frequently used filter settings do not have to be redefined each time. The most important filter set-tings such as “This Week” or “My Reports” are immediately available in a shortcut menu:To do this, right-click “Measured se-ries” in the “Reports” tabbed page. The Filter shortcut menu appears. If you choose an item from this, the corresponding filter is immediately activated (see Fig. 2).

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H. Früh

E x p e r t t i p s A p p l i c a t i o n s

Fig. 1: SevenMulti modular measurement instrument for conduc-

tivity, pH and/or ion concentration

Fig. 2: InLab®740

conductivity sensor

Control of "purified water" and "water for injection" to USP requirements

The presence of extraneous ions in water is controlled since 1996 according to the United States Pharmacopeia (USP) by measuring electrical conductivity. This article describes how the new METTLER TOLEDO SevenMulti conductivity instrument helps you meet the vari-ous analytical requirements.

The section entitled “Water for Pharmaceutical Purposes” in the US Pharmacopeia begins with the sentence: “Water is the most widely used substance, raw material, or in-gredient in the production, process-ing, and formulation of compendial articles.” (1231) [3]. And in much the same way as the Inuit use up to 100 different expressions for snow because of its vital importance for their life in the Artic, many different terms relating to water quality can also be found for water in the Pharmacopeia.

In contrast to the countless appli-cation possibilities in everyday life, drinking water is, according to the USP, only suitable for use in the ear-ly stages of chemical synthesis and in the early stages of the cleaning of pharmaceutical manufacturing equipment. Drinking water is how-ever, according to the Pharmaco-peia, the prescribed source of feed water for the production of various types of pharmaceutical waters [3]. These include: purified water, ster-ile purified water, water for injection, sterile water for injection, bacterio-static water for injection, water for rinsing and water for inhalation.These terms describe the degree of water purity obtained following the use of different operations such as deionization, distillation, ion-ex-change, reverse osmosis, ultrafiltra-tion or other procedures. The purifi-cation of drinking water to “purified water” or to “water for injection” serves not only to reduce the content of bacteria and their endotoxins, but also aims at drastically lowering the concentration of Total Organic Car-bon (TOC) and dissolved ions. In the U.S.A. the complete process of puri-fication, storage and distribution of water is governed by rules laid down by the USP (in Europe, the European Pharmacopeia) and must be backed up by a comprehensive validation and qualification program.

In view of the recent introduction of the new METTLER TOLEDO SevenMulti high precision conduc-tivity instrument (Fig. 1), we would like to take a look at the analysis procedures laid down by the USP.

Nowadays, according to the USP, extraneous ions in water are deter-mined through conductivity mea-surements. This, however, was not always the case. Up until 1996, the quality control testing of wa-ter in the pharmaceutical industry was carried out with comprehen-sive chemical measurements. The change to the much simpler conduc-tivity method necessitated a consis-tent model that allowed repre-sentative limits to be established. C onduc t i v i t y, however, is an unspecific pa-rameter that does not provide any information about the chem-ical nature of the extraneous ions. This pres-ents specialists trying to im-prove control methods with a difficult task. The reason for this is that, be-sides the extra-neous ions, the intrinsic ions H3O

+ and OH-, the atmospheric gas-es dissolved in water, in particular CO2, and also the measurement tem-perature, all play an important role. Finally one agreed to use two refer-ence systems based on the poorly conducting Cl- and NH4

+ ions for set-ting up conductivity specifications. This allowed limits (1.33 mM and 1.66 mM) [1] to be established for

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A p p l i c a t i o n s A p p l i c a t i o n s

pH Limit[µS/cm]

5.0 4.75.1 4.15.2 3.65.3 3.35.4 3.05.5 2.85.6 2.65.7 2.55.8 2.45.9 2.46.0 2.46.1 2.46.2 2.56.3 2.46.4 2.36.5 2.26.6 2.16.7 2.66.8 3.16.9 3.87.0 4.6

Fig 3: Conductivity limits for "purifi ed water" and "water for injection" according to Stage 3 USP regulations.

conductivity measurements at tem-peratures between 0 and 100 °C (see Table 1 and Fig. 3).To take into account the various re-quirements encountered in every-day processes (inline measurements and/or laboratory analyses), the USP specifi es the following three-stage procedure for conductivity control tests: [2]

Stage 1 corresponds to the most frequently encountered situation, namely measurement under ex-clusion of atmospheric gases. It consists of a non tempera-ture-compensated conductivity measurement and simultaneous temperature measurement. After-ward, one finds the temperature value in the given Conductivity/Temperature table (see Table 1) that is not greater than the mea-sured temperature. The corre-sponding conductivity value is the limit at that temperature. If the measured value is not great-er than the table value, the wa-ter meets the requirements of the test for conductivity. Stages 2 and 3 need not be performed.

Stage 2 is suitable for measure-ments where effects due to CO2 can-not be avoided. A sample of water (100 ml or more) is stirred in suit-able container at 25 ± 1 °C and the conductivity observed periodically. When the change in conductivity (due to uptake of atmospheric CO2) is less than 0.1 µS/cm per 5 minutes, the conductivity is noted. If the con-

ductivity value is not greater than 2.1 µS/cm, the water meets the re-quirements of the test for conductiv-ity and there is no need to continue to Stage 3.

Stage 3 must be performed with-in fi ve minutes of the fi nal step in Stage 2 while maintaining the sam-ple temperature at 25 ± 1 °C. A sat-urated solution of potassium chlo-ride is added to the water sample (0.3 mL/100 mL of the sample) and the pH (to the nearest 0.1 pH unit) and the conductivity measured. If the measurement values are not greater than the given limits (see Fig. 3), the water meets the require-ments of the test for conductivity (see Ref. [2] for further details).

How does SevenMulti help you meet USP requirements?SevenMulti is a new modular labora-tory instrument for the electrochem-ical determination of pH, conductiv-ity and ions. It has many important features that help you meet require-ments for measurements according to USP methods.

• Most control measurements are performed according to USP stage 1. In this method, the con-ductivity values must not be com-pensated for temperature. Seven-Multi LF has a so-called USP mode in which temperature correction can be disabled. In addition, the USP Temperature/Conductivity table (see Table 1) is stored in its internal memory. The instrument can therefore immediately indicate whether the water under test meets USP requirements.

• If your company places higher de-mands on water purity, you can enter a so-called USP factor in the instrument. The instrument then multiplies the USP values in the table with this factor and gives you your own company limits, as shown in the example in Table 1 (third column).

• Control measurements have to be performed at regular intervals. SevenMulti LF helps you to auto-mate this process.

• Working in a GLP/GMP environ-ment means that not just the mea-surement data has to be recorded, but also details such as the meth-od, the instrument and electrode used, the calibration (adjustment) data with the time and date of such calibrations, the identity of the user, etc. In the GLP mode, the Sev-enMulti LF in addition generates a detailed record and transfers this to a printer or a PC as desired.

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A p p l i c a t i o n s A p p l i c a t i o n s

Tempera-ture [°C]

Cond. Limit [µS/cm]

USP-Factori.e. 20%

0 0.6 0.12

5 0.8 0.16

10 0.9 0.18

15 1.0 0.20

20 1.1 0.22

25 1.3 0.26

30 1.4 0.28

35 1.5 0.30

40 1.7 0.34

45 1.8 0.36

50 1.9 0.38

55 2.1 0.42

60 2.2 0.44

65 2.4 0.48

70 2.5 0.50

75 2.7 0.54

80 2.7 0.54

85 2.7 0.54

90 2.7 0.54

95 2.9 0.58

100 3.1 0.62

Table 1: USP table with temperature-

dependent conductivity limits and exam-

ple for individual USP factor.

• If you perform measurements at a location where a PC or printer is not available, the internal data memory can store up to 1000 mea-surement records. The course of the measurement over a longer period of time can be displayed graphical-ly on the instrument itself.

• USP requires a resolution of 0.1 µS/cm. SevenMulti LF in fact provides 0.01 µS/cm, i.e. is a fac-tor of ten better.

• IQ/OQ: USP requires professional installation, and regular control of the operation and operability of measurement instruments. METTLER TOLEDO therefore offers qualification and/or re-certification services for the SevenMulti LF in many countries. The instrument is, in addition, equipped with a service program.

• SevenMulti LF together with the new and extremely precise In-Lab740 conductivity electrode (Fig. 2) is the ideal instrument system for the control of water quality to USP requirements.

• Official methods will no doubt change as time goes on (see fol-lowing section). The possibility of future software updates, how-ever, means that with the Seven-Multi LF you are nevertheless op-timally equipped for the future.

United States Pharmacopeia versus European Pharmaco-peiaThis year should see the definitive harmonization of the European (EP) and U.S. (USP) regulations. There are, however, still a number of obstacles to be overcome. In par-ticular, the EP sets different quality standards for “purified water” (4.3 µS/cm) and “water for injec-tion” (1.3 µS/cm), which is gener-

ally regarded as a progressive solu-tion. In contrast, the EP requires that all measurements be performed at 20 °C. This, however, practically rules out online measurements. There are also differences con-cerning the calibration of sensors. Whereas the EP specifies exactly which standard solutions have to be used, the USP defines the accu-racy via the measurement error with which the standard solutions are prepared, or via the relative error of the resistances allowed for the cali-bration (0.1 % traceable to NIST). Why the EP, in spite of conductivity measurement, still requires nitrate determination is also the subject of discussion.

METTLER TOLEDO is following all these developments with great in-terest and will make sure that the SevenMulti instrument software is always adapted to the latest require-ments specified in official regula-tions.

Literature:[1] A.C. Bevilacqua, European Jour-

nal of Parenteral Sciences, Vol. 6 No. 1 (2001), 3-11

[2] USP 26 (2003), (645) Water Con-ductivity, 2141-2

[3] USP 26 (2003), (1231) Water for Pharmaceutical Purposes, 2445-2453

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A. Aichert

A p p l i c a t i o n s A p p l i c a t i o n s

Fully automatic COD determination with the Rondo60

The HACH company uses digestion vials of smaller volume than the standard digestion vials, thereby significantly reducing the consumption of chemicals. Automated titration using these vials is also possible with the RONDO60 sample changer equipped with a modified 60-position rack. The following article presents details on this using a fully auto-mated COD determination as an example.

1. Introduction1.1. PrincipleThe chemical oxygen demand (COD) is a value that allows the quality of a water sample to be assessed. It is used for the analysis of surface water, drinking water, and wastewater in industry and private households. The COD value represents the total amount of oxidizable organic material in a water sample. This includes both biologically degradable and non-degrad-able organic material. The procedure for COD determination is described in the DIN 38409 Part 41 and ISO 6060 standards.

1.2. AnalysisThe organic content of the water sample is completely oxidized in 2 to 3 hours with an excess of potassium dichromate (K2Cr2O7) in 50% sulfuric acid (H2SO4) at 150 °C. Mercury(I) sulfate (Hg2SO4) is used to precipitate any interfering chloride and silver sulfate (Ag2SO4) added as catalyst. After the oxidation, the excess potassium dichromate is back titrated with ammonium iron(II) sulfate, (NH4)2Fe(SO4)2, FAS. This allows the amount of potassium dichromate used for the oxidation to be determined and then calculated as mg O2/L.The oxidation is performed in special COD digestion vials with a correspond-ing digestion block. The titration is performed either directly in the digestion vial or in a titration beaker following transfer of the sample.

1.3. Chemical reaction and stoichiometryThe organic content of the water sample is oxidized according to the follow-ing reaction equation: Cr2O7

2- + 14 H+ + 6e- → 2 Cr3+ + 7 H2O

After the oxidation, the excess potassium dichromate is back titrated with ammonium iron(II) sulfate:6 Fe2+ + 14 H+ + Cr2O7

2- → 2 Cr3+ + 6 Fe3+ + 7 H2O

The COD value is then calculated in mg O2/L, based on the following reac-tion equation:O2 + 2 H2O + 4e- → 4 OH-

The reduction of 1 mole of oxygen (O2) requires 4 electrons; the reduc-tion of 1 mole of dichromate, 6 elec-trons. This means that 1 mole of di-chromate corresponds to 1.5 moles of oxygen.

2. Procedure with standard digestion vialsStandard digestion vials have a round bottom, an external diameter of 38 mm and are approx. 300 mm long. Various types of digestion ap-paratus are available for these vials in which the oxidation is performed at 150 °C.

To automate the titration part of the COD determination, a special Ron-do60 COD kit is available. This al-lows titrations to be performed di-

rectly in the digestion vials using a DL5x titrator/ or DL7x titrator/Rondo60 sample changer system. The kit contains 20 digestion vials. These can be installed on the sam-ple turntable with the aid of adapt-

Fig. 1: Digestion apparatus with standard

digestion vials

18 19

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A p p l i c a t i o n s A p p l i c a t i o n s

ers. For technical reasons, the vials are somewhat shorter (200 mm) than the standard digestion vials. They also have a flat bottom so that a magnetic stirrer can be used dur-ing titration. The external diameter of the Rondo60 COD vials is 40 mm, which means that they can be used with practically all types of com-mercially available digestion ap-paratus.

3. Procedure with HACH digestion vialsThe HACH digestion vials have an external diameter of 15 mm and are 100 mm long. They are particular-ly suitable for the analysis of large numbers of samples, as usually oc-cur in water analysis laboratories. The small volume of the digestion vials is advantageous because it sig-nificantly reduces the consumption

of chemicals compared to the stan-dard digestion vials. Automated ti-tration with the Rondo60 COD kit is however not possible with these digestion vials. For this reason, the 60-position sample turntable of the Rondo60 was specially modified so that automated titration could also be performed with the HACH diges-tion vials.

3.1. Rondo60 with modified 60-position sample turntable for the HACH digestion vialsTo accommodate the HACH diges-tion vials, the diameter of the open-ings of the 60-position sample turn-table was reduced from 21 mm to 16 mm through the use of adapters (PVC tubes, wall thickness 2.5 mm). In addition, the height of the 60-po-sition sample turntable was reduced from 128 mm to 75 mm by removing a spacer block.

3.2. Design of the titration system• DL70ES with double burette drive

system for dosing dichromate and titration with ammonium iron(II) sulfate

• DM140-SC platinum ring redox electrode

• Modified 60-position sample turn-table

• Head for the 60-position sample turntable, suction tube and rins-ing tube

• Three SP250 peristaltic pumps

3.3. Measurement process1. The sample is moved to the tower,

and the head with the suction tube and the rinsing tube dipped in the HACH digestion vial.

2. The “Waste” pump empties the titration beaker.

3. The “Sample” pump transfers the contents of the HACH diges-tion vial to the titration beaker.

4. The “Water” pump fills the HACH digestion vial with 8 mL water.

5. Step 3 is repeated.6. Steps 4 and 5 are repeated three

times to ensure that the sample is completely transferred to the titration beaker.

7. Titration with ammonium iron(II) sulfate.

The dichromate burette is used for precise addition of dichromate so-lution into the HACH digestion vial prior to digestion.

Fig. 2: Rondo60 with COD kit

Fig. 3: The HACH COD reactor

Fig. 4: The modified 60-position sample

turntable of the Rondo60 for HACH

digestion vials

20 21

1 2 3 4 1 2 3Aux.Sensor

Water

FAS Na Cr O2 2 7

Sample

Rondo60

DL70ES

Waste

A p p l i c a t i o n s A p p l i c a t i o n s

3.4. Titration with ammonium iron(II) sulfate

Titer determination of ammo-nium iron(II) sulfate (FAS)Ammonium iron(II) sulfate is stan-dardized with potassium dichro-mate. It is very important that the sample is strongly acidic: 3 mL concentrated H2SO4 are added to each sample. Too little acid gives rise to an unstable measurement signal, which results in poor repro-ducibility.

Blank value determinationThree blank value determinations are performed using deionized wa-ter as the sample for each series of digestions.

Sample determinationPotassium hydrogenphthalate can be used as test substance to test the method. A concentration of 0.17 g/L potassium hydrogenphthalate (0.8325 mmol/L) corresponds to a COD value of 200 mg/L.

Fig. 5: Schematic diagram of the titration system

Mean value n srel. Deviation

Blank value 0.234649 mmol 3 0.086%

Sample COD = 213.6 214.9 mg/L 4 2.2% + 0.63%

Sample C0D = 213.6 218.8 mg/L 4 0.9% + 2.44%

Sample COD = 439.1 436.1 mg/L 4 2.6% - 0.69%

Sample COD = 439.1 436.2 mg/L 4 0.25% - 0.66%

Table 1: Blank value and sample determinations for expected COD values in the range

200 to 450 mg/L

Method for an expected COD value in the range 100 to 500 mg/L (blank value and sample determination)The follow quantities are added to a HACH digestion vial and held at 150 °C for three hours in the COD reactor.• 2.00 mL sample solution (deion-

ized water for the blank value)• 1.00 mL potassium dichromate

solution (0.04 mol/L)• 2.00 mL Ag2SO4 / H2SO4 solution

(10 g Ag2SO4 in 1000 mL concen-trated H2SO4)

• 0.2 mL Hg2SO4 (20 g Hg2SO4 in 90 mL water and 10 mL concen-trated H2SO4)

After cooling to room tempera-ture, the contents are titrated with 0.07 mol/L ammonium iron(II) sulfate.

Method for an expected COD value in the range 10 to 50 mg/L (blank value and sample determination)The follow quantities are added to a HACH digestion vial and held at 150 °C for three hours in the COD reactor.• 2.00 mL sample solution (deion-

ized water for the blank value)• 1.00 mL potassium dichromate

solution (0.01 mol/L)• 2.00 mL Ag2SO4 / H2SO4 solution

(10 g Ag2SO4 in 1000 mL concen-trated H2SO4)

• 0.2 mL Hg2SO4 (20 g Hg2SO4 in 90 mL water and 10 mL concen-trated H2SO4)

After cooling to room tempera-ture, the contents are titrated with 0.02 mol/L ammonium iron(II) sulfate.

CommentsAn equilibrium-controlled equiva-lence point titration with dynamic titrant addition is used. It is impor-tant to make sure that the potential difference per increment dE(set) does not exceed 3 mV. This ensures

20 21

A p p l i c a t i o n s A p p l i c a t i o n s

Mean value n srel. Deviation

Blank value 0.050826 mmol 3 1.0%

Sample COD = 21.4 25.48 mg/L 4 9.3% + 19.1%

Sample COD = 21.4 23.9 mg/L 3 18.1% - 12.9%

Sample COD = 21.4 17.94 mg/L 3 12.9% - 16.2%

Sample COD = 44.0 45.55 mg/L 4 3.0% + 3.5%

Sample COD = 44.0 40.73 mg/L 4 1.1% - 7.4%

Table 2: Blank value and sample determinations for expected COD values in the range

20 to 50 mg/L

that titrant addition at the equiva-lence point is performed with the smallest increment (∆Vmin).

If 0.02 moL/L ammonium iron(II) sulfate are used, the smallest vol-ume increment ∆Vmin should not be less than 0.02 mL because other-wise the measurement signal at the equivalence point is unstable. This results in poor reproducibility. For this reason, there is no sense in us-

ing a lower concentration of the ti-trant for low COD values.

3.5. ResultsWith the low COD values, the re-producibility and recovery are not satisfactory. The reason for this is the small differences in titrant con-sumption for the sample and blank value determinations. For example:Blank value = 2.6 mL, sample COD 44.0 = 2.0 mL, sample COD 21.4 = 2.3 mL

Sample preparation• Sample COD 439.1 mg/L: 0.1866 g potassium hydrogen-

phthalate dissolved in water and made up to 500 mL in the mea-suring flask.

• Sample COD 213.6 mg/L: 0.0908 g potassium hydrogen-

phthalate dissolved in water and made up to 500 mL in the mea-suring flask.

• Sample 44.0 mg/L: 10 mL sample COD 439.1 mg/L di-

luted to 100 mL with water in the measuring flask.

• Sample 22.4 mg/L: 10 mL sample COD 213.6 mg/L di-

luted to 100 mL with water in the measuring flask.

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N e w p r o d u c t s N e w p r o d u c t s

Densito 30PX, Refracto 30PX: GLP-conform documentation of measured valuesIn spite of their compactness, the portable METTLER TOLEDO instruments for the measurement of density

and refractive index offer practically all the possibilities provided by bench-top instruments: Be-sides numerous functions that ensure that the instruments are optimally adapted to the user’s needs, the Densito density meter and the Refracto refractometer have a built-in infrared interface. Both instruments can also save up to 1100 measured values (including sample identity, measure-

ment unit and temperature compensation coefficient). This allows the results to be printed or archived as an EXCEL table on a PC directly after measurement or at any time later. A suitable PC software is included as standard with the instruments.Measured values are however only fully documented if the data includes information on when (time and date) and with which instrument (identification) the measurement was performed. For this reason, the new PX versions of Densito and Refracto save the measured values togeth-

er with the time of measurement and transfer these together with an instrument identification code that can be defined by the user.

The new PX versions are in addition equipped with a backlit display. This means that measure-ments are possible onsite even under poor lighting conditions.

Available since July 2003

Refracto 30GS: the widest refractive index measurement range of hand-held instrumentsThe measuring cells of portable digital refractometers are equipped with a glass measurement prism.

The prism used in the more expensive bench-top instruments is usually made of sapphire. Sapphire has a larger refractive index and better thermal conductivity compared to glass. In addition,

sapphire is significantly more corrosion-resistant and much harder than glass. Compared with portable instruments, the measuring cells of bench-top instruments therefore usually have a wider measurement range, measure the sample temperature faster and more accu-rately, and are more resistant toward chemical and mechanical stress.With the new Refracto 30GS, METTLER TOLEDO offers a portable refractometer equipped with a sapphire measuring cell. As far as its technical specifications are concerned, the

instrument is superior to all currently available digital hand-held instruments. The Re-fracto 30GS is fully equivalent to a bench-top refractometer that is not equipped with a

thermostat.

You can learn more about our new generation of portable density meters and refractometers at www.PortableLab.com.

Available since mid September 2003

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N e w p r o d u c t s N e w p r o d u c t s

Electrochemistry in motion - SevenEasy: Plug it in, calibrate and measure pH And before you can say Jack Robinson, man and machine understand one another perfectly.

However, the title is not quite right. It’s true that with the new METTLER TOLEDO laboratory pH instrument you can measure pH and mV in the twinkling of an eye. But you don‘t necessarily have to plug in the instrument. If need be, SevenEasy works just as well with batteries. SevenEasy provides you with the full basic facilities for

routine pH measurement: 3-point calibration, and automatic buffer-recognition and temperature compensation. What else would you like? Of course, an interface for data export – with SevenEasy it’s standard.

And all this with a price-performance ratio that you’ll find irresistible.

Available since June 2003

Electrochemistry in motion - with SevenMulti, METTLER-TOLEDO is sailing right up front in the Formula One class of pH-, conductivity- and ion-measurement The latest creation from METTLER TOLEDO doesn’t have much to do with note pad and pencil: much more, however, with modern data handling, digital communication and ergonomic design. Just like in a good sailing team, SevenMulti consists of a head, the basic instrument and equal-rights assistants, and expansion units for pH, ISFET, conductivity and ion selective measurements. A concept that is unique in this field and that therefore deserves your interest. You can tailor your instrument to meet your own specific requirements and at the same time save space and costs. User comfort and comprehensive GLP support are just two of the many interesting new features on an instrument that will be of great service to any laboratory. Available since June 2003

The InLab®425 combines tradition with Innovation INGOLD has now been part of the METTLER TOLEDO group for over 17 years. The name INGOLD

stands for the success story of combined pH electrodes. The InLab® laboratory electrodes are the product of 50 years of experience in the manufacture of electrochemical sensors. This tradition

has been continued and refined with the recent introduction of the InLab®425. This electrode is a masterpiece of glassblowing skill. Its outstanding features, such as bridge electrolyte chamber, polished diaphragm, built-in temperature sensor and special membrane glass, position it unrivalled at the head of the METTLER TOLEDO range of laboratory electrodes. It’s the perfect pH electrode for:

• Emulsions • Dispersions • TRIS-buffers • Oily samples • Dairy products • Non-aqueous samples

• Samples of low ionic strength • Viscous samples • Samples of low water content • Samples of unknown composition

Available since January 2002

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P u b l i c a t i o n s

Layout and productionPromotion & Documentation, Walter K. Hanselmann© 09/2003 METTLER TOLEDO GmbH

ME-51724358

Printed in Switzerland

Printed on 100% chlorine-free paper.For the sake of our environment.

Editorial officeMETTLER TOLEDO GmbH, AnalyticalSonnenbergstrasse 74CH-8603 Schwerzenbach, SwitzerlandTel. ++41 1 806 7711Fax ++41 1 806 7240E-Mail: msganachem@mt.comInternet: http://www.titration.net

Authors: A. Aichert, Dr. Ch. Bircher, T. Butta, H. Früh, C. Gordon, P. Wyss

Publications, reprints and applications German EnglishTitration in routine and process investigations 51724658 51724659Basics of Titration 51725007 51725008Fundamentals of Titration 704152 704153Applications Brochure 1 Customer Methods 724491 724492Applications Brochure 2 Various Methods 724556 724557Applications Brochure 3 TAN/TBN 724558 724559Applications Brochure 5 Determination in Water 51724633 51724634Applications Brochure 6 Direct measurement with ISE 51724645 51724646Applications Brochure 7 Incremental Techniques with ISEs 51724647 51724648Applications Brochure 8 Standardization of titrants I 51724649 51724650Applications Brochure 9 Standardization of titrants II 51724651 51724652Applications Brochure 11 Gran evaluation DL7x 51724676 51724677Applications Brochure 12 Selected Applications DL50 51724764 51724765Applications Brochure 13 Nitrogen Determination by Kjeldahl 51724768 51724769Applications Brochure 14 GLP in the Titration Lab 51724907 51724908Applications Brochure 15 Guidelines for Result Check 51724909 51724910Applications Brochure 16 Validation of Titration Methods 51724911 51724912Applications Brochure 17 Memory card “Pulp and paper” 51724915Applications Brochure 18 Memory card “Standardization of titrants” 51724916 51724917Applications Brochure 19 Memory card “Determination in Beverages” 51725012 51725013Applications Brochure 20 Petroleum 51725020Applications Brochure 22 Surfactant Titration 51725014 51725015Applications Brochure 23 KF Titration with DL5x 51725023Applications Brochure 24 Edible oil and fat 51725054Applications Brochure 25 Pharmaceutical Industry 51710070 51710071Applications Brochure 26 METTLER TOLEDO Titrators DL31/38 * 51709854 51709855Applications Brochure 27 KF Titration with Homogenizer 51725053Applications Brochure 29 Applications with the METTLER TOLEDO Rondo 60 51710082Applications Brochure 32 METTLER TOLEDO Titrators DL32/39 51725059 51725060Applications Brochure KF Chemical 724353 724354Applications Brochure KF Food, Beverage, Cosmetics 724477 724478Applications Brochure KF 10 DL35 Applications 724325 724326Applications Brochure DL12 724521Applications Brochure DL18 724589 724590Applications Brochure DL25 724105 724106Applications Brochure DL25 Food 51724624 51724625Applications Brochure DL25 Petro / Galva 51724626 51724627Applications Brochure DL25 Chemical 51724628 51724629Applications Brochure DL70 Gold and Silver 724613

* Also available in French (51709856), Spanish (51709857) and Italian (51709858)

The application chemists of the Analytical Chemistry market support group have prepared several publications and a series of applica-tion brochures to support customers in their routine work in the laboratory. Each brochure is dedicated either to a particular branch of industry (such as paper, petroleum and beverages), a particular titrator or a specific analysis technique. The following list shows all the publications together with their order numbers. They are available from your local METTLER TOLEDO marketing organization.