83Innovations in Pharmaceutical Technology

Manufacturing

In the drive for accuracy and to achieve lower detectionlimits, the pharmaceutical and biotech industries arefinding that a new ultra-pure form of hydrogen is theoptimum grade for analytical applications. But what isdriving this demand for accuracy and why is this newgeneration hydrogen proving so popular?

PURITY – A TECHNOLOGICAL SOLUTIONIn a bid to improve analytical accuracy of gaschromatography detection applications for thepharmaceutical industry, an innovative technology hasbeen applied (BIP® Tecnology) to deliver an exceptionalultra-high purity gas product, with critical impurities suchas oxygen, water and hydrocarbons dramatically reducedcompared with conventional grades. Fitted with aninternal purifier and patented valve system, the technologyeffectively ensures that the gas meets the highest standardof purity at the point of use, every time it is used.

This technological development could make a big differenceto analytical processes and provide a further assurance of quality. For the pharmaceutical analyst, using the ultra-high purity hydrogen will significantly lower detection levels and provide an assurance of improved accuracy.

THE ROLE OF HYDROGEN IN GAS ANALYSISHydrogen is not new to gas chromatography (GC), and inthe pharmaceutical processing industry it has been used fordecades both as a carrier gas in GC/GC-MS (massspectrometry) and as a detector fuel gas for flame ionisationdetector (FID), nitrogen phosphorus detector (NPD) andflame photometric detector (FPD). These methods of gaschromatography detection are particularly well suited topharmaceutical manufacturing because they are verysensitive and capable of giving accurate readings of complex samples containing a large number ofcomponents at low concentrations. This kind of gas analysisis a critical part of the manufacture of any modern drug andis carried out at every stage of the production process.

Hydrogen as a detector fuel gas in FID, NPD and FPDapplications is used to produce the flame that convertsthe sample into electrically charged ions that produce the required electrical signals that generate thechromatograph. However to date, the analytical accuracyand limits of detection achievable have been limited bythe purity of the hydrogen and air that is commerciallyavailable. For optimum analytical results, it is importantto use the highest grade of gas possible, with a low totalhydrocarbon (THC) content.

When the purity of the hydrogen or air used in a GC-FIDapplication falls short of the quality needed for such gasanalysis, it results in a phenomenon known to chemists as‘baseline noise’ – the appearance of unwanted peaks on thechromatogram. These imperfections can make it virtuallyimpossible to measure the area beneath the peaksaccurately. For the pharmaceutical analyst, this means thatit may not be possible to detect some components in thesample at all, simply because they are present at very lowconcentrations that are below the limit of detection.

DELIVERING IMPROVED ACCURACYIn the ongoing drive for improved accuracy andtraceability, these imperfections are no longer acceptable,

Gas Analysis – the Hydrogen WayA new ultra-pure form of hydrogen is finding application in a range of gaschromatography methods – increasing analytical accuracy, improving limits ofdetection and extending use of the technique in pharmaceutical processing.

By Lieve de Paepe at Air Products

Lieve de Paepe joined Air Products in 1990 after graduating as a Chemical Engineer from the University of Ghent (Belgium). In her current role, she is responsible for supporting the development of specialitygases for a wide range of industrial applications in the pharmaceutical, chemical and environmentalmanagement sectors.

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and the pharmaceutical and biotech industries aredemanding quality gas products that are capable ofproducing highly accurate analyses and improved limits ofdetection, time after time.

Responding to this drive for improved accuracy andtraceability, many pharmaceutical analysts are alreadysourcing gas products that come with an assurance ofquality. When using gas calibration mixtures, for example,most analysts prefer to use speciality gases supplied by anISO 17025 accredited laboratory, such as the rangeproduced by Air Products, which includes productsaccredited to ISO 17025 by the Entidad Nacional deAccreditacion (ENAC) in Spain. Similarly, when usingpure gases – such as nitrogen, helium or hydrogen – foruse in gas chromatography or production processes, ultra-high purity is preferred. Until now, however, this optionhas not been available when sourcing hydrogen.

EXTENDING THE BENEFITSA recent survey by LCGC Europe has revealed that 73 percent of the problems that arise in GC analysis are due toimpurities in the carrier gas. Such impurities are typicallywater and oxygen, and they need only be present at verylow levels to affect the accuracy and reliability of analyses.

In order to eliminate this problem, pharmaceuticalmanufacturers are increasingly using higher purity gasesand, currently, the carrier gas of choice is helium, whichprovides fast analysis combined with a high level ofanalytical accuracy. As a carrier gas, helium compares veryfavourably with nitrogen which, while lower in cost,results in much slower analysis.

However, the arrival of ultra-high purity BIP® hydrogenpresents an opportunity for some pharmaceuticalmanufacturers to further improve accuracy. While mostusers are highly satisfied with helium, switching tohydrogen can provide analytical results that are even moreaccurate. There is another benefit too – using hydrogen as

a carrier gas can deliver analytical results more quickly,with a timesaving that can be as high as 35 per cent.

HYDROGEN – A NEW CARRIER GAS?Despite the potential improvements with hydrogen, heliumis likely to remain the carrier gas of choice for thepharmaceutical and biotech industries mainly because it isinert and delivers accurate results. However, in certainanalytical applications, the efficiencies that could be attainedby switching to hydrogen as a carrier gas are difficult toignore. In such circumstances, using hydrogen has recentlybecome all the more viable due to the safety features thathave been introduced to modern gas chromatographs, suchas flow rate monitors that will automatically shut-down thehydrogen supply if a leak is detected. The introduction ofthese safety features, combined with the availability of ultra-high purity BIP® hydrogen gas, is encouraging a growingnumber of analytical users to consider using hydrogen as acarrier gas for the first time.

For some pharmaceutical manufacturers, there may even bebenefits from using the new ultra-high purity hydrogen forhydrogenation. In such instances, hydrogen is used as a rawmaterial in a chemical reaction as a step in a drugmanufacturing process, and the use of purer hydrogen gasproduct may well be beneficial.

THE HYDROGEN OPPORTUNITYThe cumulative effect of these recent developmentspresents an opportunity for pharmaceutical manufacturersas they look for ways to increase analytical accuracy,improve limits of detection and produce ever moresophisticated drugs and treatments. As a detector fuel gasfor FID, NPD and FPD applications, the new ultra-highpurity BIP® hydrogen alternative is already attractingsignificant interest internationally, and the potential of itsbenefits has yet to be fully explored.

The author can be contacted atdepaepel@airproducts.com

84 Innovations in Pharmaceutical Technology

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