CCQM-K11.1: Subsequent Key Comparison on the...

1

CCQM-K11.1: Subsequent Key Comparison on the Determination of

Glucose in Serum

Final Report

September 2006

Lian Hua Shi, Byung-Joo Kim, Hwa-Shim Lee, and Sang-Ryoul Park

Korea Research Institute of Standards and Science (KRISS)

Daejeon, Korea

Marco Antonio Avila Calderón and Melina Pérez Urquiza

Centro Nacional de Metrología (CENAM)

Querétaro, México

Hisashi Kato

National Metrology Institute of Japan (NMIJ)

Tsukuba, Japan

Can Quan and Hongmei Li

National Research Center for Certified Reference Materials (NRCCRM)

Beijing, China

INTRODUCTION

The accuracy and traceability of routine clinical diagnostic tests has become a matter of

great concern. Inconsistency in test results due to the lack of high quality measurement

standards implemented in clinical practices often leads to confusion in making medical

decisions as well as unnecessary and costly repeats of tests. This problem has been

legally addressed by the European Union to implement of an In-vitro Diagnostic (IVD)

Directive. Other parts of the world are likely to follow the EU in requiring greater

traceability for IVD products. Upon this change, CIPM, IFCC, and several other related

international organizations have organized the Joint Committee on Traceability in

Laboratory Medicine (JCTM) to help implementation of measurement standards in the

2

field of laboratory medicine [1]. National metrology institutes (NMIs) are to take great

responsibility in development and dissemination of measurement standards of higher

order. Therefore, Key Comparisons of substances of great diagnostic values have been

actively organized and carried out under CCQM.

Glucose is one of the most frequently measured substances in human blood. Although

various measurement methods have been established and applied, the accuracy of the

clinical tests is still of great concern. Therefore, providing measurement standards based

on a primary reference method is an important matter. In 2002, Organic Analysis

Working Group (OAWG) of CCQM had performed a key comparison of determination

of glucose in human serum in which three NMIs (NIST, KRISS, PTB) had participated

and demonstrated their capability for determination of glucose in human serum. The

results of the KC are available from the BIPM KCDB [2].

There were other NMIs who needed to demonstrate their measurement capabilities in

determination of glucose in human serum in a form of CCQM Key Comparison.

Considering the situation, the chair of OAWG arranged a Subsequent Key Comparison

(CCQM-K11.1). Under the guidance of OAWG, KRISS who demonstrated its

measurement capability in CCQM-K11 coordinated the Subsequent Key Comparison.

CENAM (Mexico), NMIJ (Japan), NRCCRM (China), and VNIM (Russia) participated

in the Subsequent Key Comparison, and two sets of test materials representing normal

and elevated glucose levels in human serum were sent. All participants except VNIM

successfully returned measurement results. Returned data were presented in OAWG

Fall meeting of 2005 with minimum data processing, and no significant comments on

the results of the Subsequent Key Comparison were made by OAWG. In the final report,

modifications of initially reported expanded uncertainties were made as NRCCRM and

KRISS found needs for correction in their assessments. As not allowed, no modification

was made in the initially reported mean values.

The draft of the final report was submitted to the 2006 April meeting of OAWG,

OAWG decided to place the originally reported expanded uncertainties by participants

as the final values. This recommendation has been reflected in the revised report.

Corrections of some miscalculations in the previous draft repro were also made.

3

SUMMARY OF ORIGINAL CCQM-K11 STUDY

A Key Comparison on the determination of glucose in human serum, CCQM-K11 was

conducted in 2002 with National Institute of Standards and Technology (NIST) as the

coordinating laboratory. Two laboratories participated in this Key Comparison:

Country Institution

Korea Korea Research Institute of Standards and Science, KRISS

Germany Physikalisch-Technische Bundesanstalt, PTB

USA National Institute of Standards and Technology, NIST (Pilot Lab)

The details of the study outcome can be found at the BIPM website [2]. The conclusion

of the study was that the participating NMIs demonstrated the ability to make accurate

and precise measurements of glucose in human serum with the exception of Material II

of the KC. The essential part of the results of this study is presented in Table 1.

CONDUCT OF THIS STUDY (CCQM-K11.1; CCQM-K11-Subsequent)

Participants

The following five countries participated in this study:

Country Institution

China National Research Centre for Certified Reference Materials, NRCCRM

Japan National Metrology Institute of Japan, NMIJ

Korea KRISS (Coordinating Laboratory)

Mexico National Center of Metrology, CENAM

Russia D.I. Mendeleyev Institute for Metrology, VNIM (data not returned)

VNIM had received test materials, but could not perform measurements due to the lack

of resources. KRISS is the only laboratory participated in CCQM-K11 and had

demonstrated capability for accurate measurement of glucose in human serum.

Therefore, KRISS, the coordinating laboratory was to provide a link to CCQM-K11 for

the results of this study.

4

Methods Used for the CCQM-K11-Subsequent Comparison

VNIM unfortunately could not perform measurement at this time due to the lack of

resources. The laboratories chose to use either GC/ID-MS or LC/ID-MS. KRISS used

ultra-filtration with 3000 Da cut-off filters for removal of proteins. Other laboratories

used ethanol precipitation. Three laboratories used NIST SRM917b as the high purity

glucose for preparation of standard solutions. NRCCRM used a product from Amresco

Inc. of which purity was claimed to be 99.8 %. CENAM and KRISS performed

validation of the measurements with CRM DMR-263a and NIST SRM 965a, respectively.

Table below is the summary of the methods used by each laboratory.

Laboratory Sample prep. &

derivatization

Measurement Calibration

material

Validation

CENAM Ethanol precip. &

NH4OH derive.

GC/ID-MS NIST SRM917b CRM DMR-

263a

KRISS Ultra-filtration

(3000 Da)

LC/ID-MS NIST SRM 917b NIST SRM 965a

NMIJ Ethanol. percip.

LC/ID-MS NIST SRM 917b

NRCCRM Ethanol precip. &

NH4OH derive.

GC/ID-MS Amresco*,

99.8%

VNIM Not ready to perform

analysis

NA NA NA

* The Amresco Inc. product was supplied without uncertainty certification.

Materials Used for the CCQM-K11-Subsequent Comparison

Candidate certified reference materials of human serum prepared by KRISS were used

as test materials in this study. The test materials were natural human serum to which no

preservative was added. Only antiseptic filtering and/or fortification were applied.

Homogeneity of glucose levels was estimated 0.4 % RSD for both test materials as

presented in the figure below.

5

Target ranges were given as follows:

01A 02A

Glucose 1100 – 1400 mg/kg 600 – 900 mg/kg

0 2 4 6 8 10

0.96

0.98

1.00

1.02

1.04

De

via

tio

n

Vial number

0 2 4 6 8 10

0.96

0.98

1.00

1.02

1.04

De

via

tio

n

Vial number

01A 02A

Results of homogeneity test of the test materials for glucose measurement.

The test materials were to be kept frozen (either at -20 oC or at -70

oC ). However, no

visible sign of degradation was observed during storage at room temperature for several

weeks as far as the seals were intact. Each test material consisted of 4 vials of 3 mL of

human serum. For the set of 4 vials, one is for practice and/or for better determining the

target concentration whereas the rest 3 vials are for measurement. The test materials

were sent as packed with a sufficient amount of dry ice to keep them frozen for several

days. However, test materials sent to VNIM and to NRCCRM were exposed to ambient

temperature for more than 10 days because of trouble at custom offices. KRISS

performed measurements with test materials exposed to room temperature for 20 days

and found no significant difference from the measurement results with normally stored

materials. Based on this result, NRCCRM performed the measurements without

replacement of originally received test materials.

Extra care needed to be taken to avoid microbial consumption of glucose as soon as the

test materials are exposed to ambient air. Immediate spiking of an appropriate antibiotic

agent was recommended.

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Measurement Protocol and Calculation of Uncertainty

As requested, all participants except VNIM produced two independent results from each

vial of a test material. Three vials of a test material were distributed. Therefore, 6

measurements were resulted from each test material. The results were to be reported on

an absolute basis (corrected for chemical purity of the calibration material used by the

participant) together with the expanded uncertainty. Space was provided at the end of

the data reporting sheets for inclusion of a full uncertainty budget, including definition

of terms and assessment of which components made significant contributions.

Linking the Subsequent Key Comparison to the Original Key Comparison

The results of CCQM-K11-Subsequent were initially treated as if an independent Key

Comparison was carried out (Table 2-1 & 2-2). Then, liking them to the results of the

original Key Comparison was made by applying proportionality factors obtained

through comparison of KRISS results from both Key Comparisons. KRISS results from

the Subsequent Key Comparison were assumed to have the same fractions of deviation

from KCRVs (virtual values) as determined in the original Key Comparison. From this

assumption, KCRVs of the Subsequent Comparison were assigned as noted as assigned

KCRVs in Table 3. One problem was that KCRV was not determined for the elevated

level of glucose (Material II). Considering the closeness of glucose concentrations in

two test materials, assigned KCRV for Test Material 01A was also calculated by

comparing the results to those for Material I of CCQM-K11. Calculation of the assigned

KCRVs is shown bellow.

Assignment of the KCRV for Test Material 01A of K11.1:

Assigned KCRV = 1248.7 mg/kg x (776.2/775.3) = 1250.1 mg/kg

776.2 mg/kg: KCRV for Material I of CCQM-K11;

775.3 mg/kg: KRISS result for Material I of CCQM-K11;

1248.7 mg/kg: KRISS result for Test Material 01A of CCQM-K11.1

Assignment of the KCRV for Test Material 02A of CCQM-K11.1:

Assigned KCRV = 779.90 mg/kg x (776.2/775.3) = 780.81 mg/kg

776.2 mg/kg: KCRV for Material I of CCQM-K11;

775.3 mg/kg: KRISS result for Material I of CCQM-K11;

779.9 mg/kg: KRISS result for Test Material 02A of CCQM-K11.1

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Originally, expanded uncertainties were also linked to the results of original Key

Comparison in the same manner as applied for calculation of deviations of from KCRVs.

Calculation of adjusted uncertainties are shown below.

Adjustment of expanded uncertainties for Test Material 01A

Adjusted Uncertainties = Reported uncertainties x (1.41/0.897)

1.41 %: KRISS Rel. Uncertainty (%) for Material I of CCQM-K11;

0.897 %: KRISS Rel. Uncertainty (%) for Test Material 01A of CCQ-K11.1

Adjustment of expanded uncertainties for Test Material 02A

Adjusted Uncertainties = Reported uncertainties x (1.41/0.907)

1.41 %: KRISS Rel. Uncertainty (%) for Material I of CCQM-K11;

0.907 %: KRISS Rel. Uncertainty (%) for Test Material 02A of CCQ-K11.1

During the CCQM meeting in April 2006, Organic Analysis Working Group decided to

accept the originally reported expanded uncertainty by each participating laboratory as

the final values of the expanded uncertainty. Therefore, the values calculated above for

linking to the original study were not taken as the final values.

RESULTS

Results for the CCQM-11-Subsequent Comparison are summarized in Table 2. The

uncertainty bars in the figures represent expanded uncertainties as reported by the

participating laboratories. Uncertainties in the results of NRCCRM were changed from

the values reported in OAWG fall meeting 2005 as requested by NRCCRM. KRISS

also refined its uncertainty budgeting procedure and made minor modifications of

originally reported uncertainties. Evaluation of uncertainty reported by each laboratory

is summarized in Table 5. The results of linking the results of this Subsequent Key

Comparison to the original Key Comparison are presented in Table 3. As decided by

OAWG, the uncertainties originally reported by participants were placed as the final

values regardless the results of linking to the results of CCQM K-11.

DISCUSSION

KRISS is the only laboratory participated in the original CCQM-K11 Key Comparison

[2]. KRISS, the coordinating laboratory, is to provide a link to the results of the original

Key Comparison for the results of this Subsequent Key Comparison. KRISS proved its

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capability for accurate measurement of glucose in human serum in the original Key

Comparison study. In addition, KRISS validated its measurement procedure by

performing simultaneous measurement of NIST SRM 965A as shown below.

1193.58 ± 21.56KRISS measurement

1192.97 ± 12.7122.1 ± 1.3Certified value

mg/kgmg/dLLevel 3


766.60 ± 8.3978.50 ± 0.86Certified value

mg/kgmg/dLLevel 2

NIST SRM 965a

(frozen serum)


1192.97 ± 12.7122.1 ± 1.3Certified value

mg/kgmg/dLLevel 3


766.60 ± 8.3978.50 ± 0.86Certified value

mg/kgmg/dLLevel 2

NIST SRM 965a

(frozen serum)

It was unfortunate that VNIM could not perform measurements because of insufficient

resources for the moment. CENAM’s results showed good agreement with KRISS

results for both test materials. It might not be a pure coincidence that both laboratories

validated their measurement procedures using reference materials. NRCCRM’s result

showed a good agreement with the results of CENAM and KRISS for Test Material

01A but produced significantly lower mean value with a relatively larger uncertainty for

Test Material 02A. NMIJ reported substantially higher mean values for both test

materials with substantially larger uncertainties (Table 2).

Homogeneity of test materials should not be a major factor for scattering of the data

(especially NMIJ’s results) because the results of measurement of three vials were

relatively close to each other (0.2-0.5 % RSD) in the results of CENAM, KRISS, and

NRCCRM (see Figure below). The vials were randomly chosen from the pools of

several thousand vials. Substantial scattering of NMIJ’s data for Test Material 02A

(1.6% RSD) is also noticeable. NMIJ may need to validate the measurement procedure

applied to this study.

9

1200

1250

1300

1350

1400

Glu

co

se

(m

g/k

g)

760

780

800

820

840

860

Glu

co

se

(m

g/k

g)

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

Test Material 01A Test Material 02A

1200

1250

1300

1350

1400

Glu

co

se

(m

g/k

g)

760

780

800

820

840

860

Glu

co

se

(m

g/k

g)

1200

1250

1300

1350

1400

Glu

co

se

(m

g/k

g)

760

780

800

820

840

860

Glu

co

se

(m

g/k

g)

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

Test Material 01A Test Material 02A

NRCCRM’s mean value for Test Material 02A is substantially deviated from the result

of KRISS. With the help of the relatively large expanded uncertainty, however,

NRCCRM’s result was in agreement with the results of CENAM and KRISS. It may

still be a serious matter that NRCCRM used a high purity standard material without

certification of uncertainty.

After conversion of the reported values of this study to get linked to the original Key

Comparison study, % deviations of CENAM, NMIJ, and NRCCRM’s results from the

assigned KCRV of Test Material 01A were 1.1 %, 9.6 %, 0.85 %, respectively. NMIJ ‘s

result was absolutely deviated. Other two labs’ results were also relatively largely

deviated compared to the maximum deviation of 0.5 % of CCQM-K11. However, these

results were in agreement within the expanded uncertainties. The relative expanded

uncertainty of CENAM’s measurement was comparable to that of PTB’s result of

CCQM-K11 (1.4 % vs. 1.4 %). The relative expanded uncertainty of NRCCRM’s

measurement is significantly larger (2.3 %).

10

CONCLUSIONS

In this study, CCQM-11.1 Key Comparison, CENAM and NRCCRM demonstrated

their ability in measurement of glucose in human serum at both clinically normal level

and elevated level in. The degrees of equivalence demonstrated in this study (%U: 2.8 –

6.9 %) were significantly inferior to that of the original Key Comparison (%U: 1.13 %).

Inclusion of NRCCRM data for Test Material 02A needs to be discussed by OAWG.

Exposure to ambient temperature for an extended time period (~ 2 weeks) might

partially contribute to the substantially underestimating result of NRCCRM. Regardless,

NRCCRM seems to need to improve the measurement uncertainty to the level that other

NMIs showed in CCQM-K11 and its subsequent comparison. In addition, NRCCRM

has to establish an uncertainty in determination of the purity of its high purity standard

material or to use a material provided with certification of uncertainty to have

appropriate measurement traceability to SI unit. NMIJ reported substantially elevated

results for both test materials. NMIJ needs to find the sources of the substantial bias and

validate its measurement procedure using a reliable reference material.

REFERENCES

[1] http://www.bipm.org/en/committees/jc/jctlm/

[2] http://www.bipm.org/utils/common/pdf/final_reports/QM/K11/CCQM-K11.pdf.

http://www.bipm.org/utils/common/pdf/final_reports/QM/K11/CCQM-K11.pdf

11

Table 1-1. Results of CCQM-K11 Glucose in Human Serum: Material I

Units: mg/kg

Participant Mean Standard U

ncertainty

Degrees of

freedom

k Expanded

uncertainty

KRISS 775.3 3.4 2.9 3.180 10.9

NIST 780.1 4.1 357 1.967 8.1

PTB 773.2 2.5 2 4.303 10.8

Mean: 776.2

Std dev of mean: 2.04

Degrees of Freedom: 2

K factor: 4.303

U: 8.8

U(rel) %: 1.1%

KCRV: 776.2 mg/kg 8.8 mg/kg

(treated as an independent study)

Table 1-2. Results of CCQM-K11 Glucose in Human Serum: Material II

Units: mg/kg

Participant Mean Standard U

ncertainty

Degrees of

freedom

k Expanded

uncertainty

KRISS 1455.9 24.90

NIST 1474.4 15.32

PTB 1514.6 18.18

Mean: 1494.5



K factor: 4.303

U: 70.6

U(rel) %: 4.72%

KCRV Undetermined

12

Table 2-1. Results of CCQM-K11.1 Glucose in Human Serum: Test

Material 01A

Units: mg/kg

Participant Mean Standard

Uncertainty

Degrees of

freedom

k Expended

uncertainty

CENAM 1264 8.3 13* 2.16 18

KRISS 1249 5.5 31 2.04 11

NMIJ 1370 8.0 35* 2.03 16

NRCCRM 1261 15 1000* 1.96 29

VNIM N/A N/A N/A N/A N/A * The unreported degrees of freedom were assigned by the coordinating lab based on the reported k value.

NMIJ data were excluded in the following calculations.

Mean: 1258



K factor: 4.30 (95% confidence level)

U: 35

Relative U (%): 2.8

KCRV 1258 mg/kg 35 mg/kg


1200

1250

1300

1350

1400

Glu

co

se (

mg

/kg

)

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

13

Table 2-2. Results of CCQM-K11.1 Glucose in Human Serum: Test

Material 02A

Units: mg/kg

Participant Mean Standard

Uncertainty

Degrees of

freedom

k Expanded

uncertainty

CENAM 786.1 4.3 13* 2.31 9.6

KRISS 779.9 3.5 31 2.04 7.1

NMIJ 834.5 11 35* 2.03 23

NRCCRM 762.1 9.2 1000* 1.96 18

VNIM N/A N/A N/A N/A N/A * The unreported degrees of freedom were assigned by the coordinating lab based on the reported k value.

NMIJ data were excluded in the following calculations.

Mean: 776



K factor: 4.30 (95% confidence level)

U: 54

Relative U (%): 6.9

KCRV 776 mg/kg 54 mg/kg


CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

720

740

760

780

800

820

840

860

Glu

co

se

(m

g/k

g)

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

720

740

760

780

800

820

840

860

Glu

co

se

(m

g/k

g)

14

Table 3-1. Link to the original study: Test Material 01A (elevated glucose

level)

Units: mg/kg; Linked KCRV = 1250.1 (See page 6)

Participant Mean of

K11.1

Difference

from

KCRV

% Difference

from KCRV

% Rel.

uncertainty, K11.1

(Linked to K11)***

Finalized

rel.

uncertainty

(%)

CENAM 1264 14 1.1 1.4 (2.2) 1.4

KRISS 1248.7 -1.4 -0.11 0.90 (1.4) 0.90

NMIJ 1369.5 120 9.6 1.3 (1.9) 1.3

NRCCRM 1261 11 0.85 2.3 (3.7) 2.3

NIST 0.50* 1.0

**

PTB -0.39* 1.4

**

* % difference in CCQM-K11;

** relative expanded uncertainty in CCQM-K11;

*** % relative uncertainty

calculated as linked to the results of CCQM-K11 assuming the uncertainty of KRISS was exactly

maintained.

-4

-2

0

2

4

6

8

10

12

% D

iffer

ence

from

KC

RV

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

KR

ISS

NIS

T

PT

B

K-11 K-11.1

-4

-2

0

2

4

6

8

10

12

% D

iffer

ence

from

KC

RV

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

KR

ISS

NIS

T

PT

B

K-11 K-11.1

15

Table 3-2. Link to original study: Test Material 02A (normal glucose level)

Units: mg/kg; Linked KCRV = 780.81 (See page 6)

Participant Mean of

K11.1

Difference

from

KCRV

% Difference

from KCRV

% Rel.

uncertainty, K11.1

(Linked to K11) ***

Finalized

rel.

uncertainty

(%)

CENAM 786.1 5.3 0.68 1.2 (1.9) 1.2

KRISS 779.9 -0.9 -0.12 0.91 (1.4) 0.91

NMIJ 834.5 53.7 6.9 3.0 (4.3) 3.0

NRCCRM 762.1 -18.7 -2.4 2.3 (3.8) 2.3

NIST 0.50* 1.0

**

PTB -0.39* 1.4

**

* % difference in CCQM-K11;

** relative expanded uncertainty in CCQM-K11;

*** % relative uncertainty

calculated as linked to the results of CCQM-K11 assuming the uncertainty of KRISS was exactly

maintained.

-10

-8

-6

-4

-2

0

2

4

6

8

10

12

% D

iffer

ence

from

KC

RV

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

KR

ISS

NIS

T

PT

B

K-11 K-11.1

-10

-8

-6

-4

-2

0

2

4

6

8

10

12

% D

iffer

ence

from

KC

RV

CE

NA

M

KR

ISS

NM

IJ

NR

CC

RM

KR

ISS

NIS

T

PT

B

K-11 K-11.1

16

Table 4-1. Uncertainty Reports: Test Material 01A (CENAM)

Uncertainty Budget (Sources of uncertainty, their type, evaluation and magnitude)

Parameter Source of

uncertainty

xi u(xi)

f

xu x

i

i

( )

Degrees of

freedom

(i)

Type Source of

data

Method

precision

Between batch

precision for the

method as a whole

(major source)

1264,4 6.4 1 5 A

Replicate

analysis of

sample

across two

batches

Calibration

solution

Concentration of

the calibration

solution (corrected

for purity) (major

source)

1254,1 2,5 1 large B Supplier’s

specification

Weight of

sample

Balance linearity

(minor source) 1.00535 0,00016 1 large B

Balance

calibration

certificate

Weight of

calibration

compound

Balance linearity

(minor source) 1,00688 0,00005 1 large B

Balance

calibration

certificate

Sample

response in

GC-MS

Area ratio of

unlabeled/labeled

glucose in sample

(Major source)

1,0234 0,0018 1 3

Repeatibility

of sample

injection

Calibration

solution

response in

GC-MS

Area ratio of

unlabeled/labeled

glucose in

calibration

compound (Major

source)

1,0221 0,0021 1 3

Repeatibility

between

calibration

injection

Other

Other

17

Table 4-2-A. Uncertainty Reports: Test Material 01A (KRISS)


Parameter Source of

uncertainty

xi u(xi)

f

xu x

i

i

( )

Degrees of

freedom

(i)

Type Source of

data

Method

precision

Between batch

precision for the

method as a

whole (major

source)

1248.7

mg/kg

1.0278

mg/kg

~ 1 5 A Replicate

analysis of

sample

across tree

samples

Calibration

solution

Purity correction

(major source)

99.7% 0.2% ~ 1 large B Certified

value from

SRM

Provider

Weight of cal.

compound

126.58

mg

0.4

mg

~ 1 large B Calibration

certificate

Weight of cal.

solution

19.9021

g

0.4

mg


certificate

Standard

Solution

Accuracy in prep.

of std soln.

0.9965

0.000971

~ 1 3 A Std dev of

R.F. of 4

std solns

u

(Mis_sol,std/Ms_sol,std)

0.94007

0.00069 ~ 1 large B Calibration

certificate

Sample

solution

u

(Mis_sol,std/Ws)

0.56935

0.00011


certificate

Random components were counted in method precision.

ARstd Repeatability

of determination

0.98900

0.00173

~ 1 4 A Replicate

analysis of

std. soln.

ARsample Counted in method precision

18

Table 4-2-B. Uncertainty Reports: Test Material 02A (KRISS)


Parameter Source of

uncertainty

xi u(xi)

f

xu x

i

i

( )

Degrees of

freedom

(i)

Type Source of

data

Method

precision

Between batch

precision for the

method as a

whole (major

source)

779.90

mg/kg

3.472

mg/kg

~ 1 5 A Replicate

analysis of

sample

across tree

samples

Calibration

solution

Purity correction

(major source)

99.7% 0.2% ~ 1 large B Certified

value from

SRM

Provider

Weight of cal.

compound

126.58

mg

0.4

mg


certificate

Weight of cal.

solution

19.9021

g

0.4

mg


certificate

Standard

Solution

Accuracy in prep.

of std soln.

0.9965

0.000971

~ 1 3 A Std dev of

R.F. of 4

std solns

u

(Mis_sol,std/Ms_sol,std)

0.94007

0.00069 ~ 1 large B Calibration

certificate

Sample

solution

u

(Mis_sol,std/Ws)

0.36348

0.00011


certificate

Random components were counted in method precision.

ARstd Repeatability

of determination

0.98900

0.00173

~ 1 4 A Replicate

analysis of

std. soln.

ARsample Counted in method precision

19

Table 4-3. Uncertainty Reports: Test Material 01A & 02A (NMIJ)

Value Uncertainty, u(xi) degree of freedom Type of uncertainty

Sample preparation

01A 1369.5 4.37 2 A

02A 834.45 5.29 2 A

Vial subdivision

01A 1369.5 4.43 6 A

02A 834.45 6.26 6 A

LC－MS measurement

01A 1369.5 3.16 36 A

02A 834.45 4.00 36 A

Calibration solution purity(NIST SRM-917b) １)

0.997 0.115 inf B

Weight of sample. １)

Ws(01A) 0.93305 (g) 0.000016 (g) inf B

Ws(02A) 1.00482 (g) 0.000016 (g) inf B

Weight of the standard compounds taken for preparation of calibration solution. １)

Wc(917b) 100.61 (mg) 0.016 (mg) inf B

Weight of internal standard solution１)

.

Ws(01A) 15.21 (mg) 0.016 (mg) inf B

Ws(02A) 8.71 (mg) 0.016 (mg) inf B

1) Supposed to be rectangularly distributed.

20

Table 4-4-A. Uncertainty Reports: Test Material 01A (NRCRM)


Parameter Source of

uncertainty

xi

u(xi)

f

xu x

i

i

( )

Degrees

of

freedom

(i)

Type Source of

data

Method

precision

Between

batch

precision for

the method as

a whole

(major

source)

1260.8mg/kg 1.138mg/kg 1.14mg/kg 5 A

Replicate

analysis of

sample across

two batches

RAS 1.0226

RAL 0.9835

RAH 1.0706

Calibration

solution

Concentration

of the

calibration

solution

(corrected for

purity) (major

source)

1266.5mg/kg 12.69mg/kg 12.9mg/kg large B Supplier’s

specification

Weight of

calibration

compound

Balance

linearity

(minor

source)

1.5593mg 0.05774g 0.0476g large B

Balance

calibration

certificate

Weight of

sample

Balance

linearity

(minor

source)

0.09600g 27.71g 0.372mg/kg large B

Balance

calibration

certificate

21

Table 4-4-B. Uncertainty Reports: Test Material 02A (NRCRM)


Parameter Source of

uncertainty

xi

u(xi)

f

xu x

i

i

( )

Degrees

of

freedom

(i)

Type Source of

data

Method

precision

Between

batch

precision for

the method as

a whole

(major

source)

762.08mg/kg 0.6738mg/kg 0.674mg/kg 5 A

Replicate

analysis of

sample

across two

batches

RAS 1.0563

RAL 0.9852

RAH 1.0774

Calibration

solution

Concentration

of the

calibration

solution

(corrected for

purity) (major

source)

742.75mg/kg 7.443mg/kg 7.97mg/kg large B Supplier’s

specification

Weight of

calibration

compound

Balance

linearity

(minor

source)

0.8858mg 0.05774g 0.0518mg/kg large B

Balance

calibration

certificate

Weight of

sample

Balance

linearity

(minor

source)

0.09385g 27.09g -0.230mg/kg large B

Balance

calibration

certificate

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