Primary standardization of assays for anticonvulsant drugs: comparison of accuracy and precision

J.F. Wilson, I.D. Watson, J. Williams, P.A. Toseland, A.H. Thomson, G. Sweeney, B.L. Smith, L.N. Sandle, J.D. Ramsey, N.E. Capps

Research output: Contribution to journalArticle

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Abstract

Background: The accuracy and precision of methods for the measurement of the anticonvulsants phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide, and valproate in human serum were assessed in 297 laboratories that were participants in the United Kingdom National External Quality Assessment Scheme (UKNEQAS).

Methods: We distributed lyophilized, serum-based materials containing low, medium, and high weighed-in concentrations of the drugs. The 297 participating laboratories received the materials on two occasions, 7 months apart. Expected concentrations were determined by gas chromatography or HPLC methods in five laboratories using serum-based NIST reference materials as calibrators.

Results: In general, bias was consistent across concentrations for a method but often differed in magnitude for different drugs. Bias ranged from −1.9% to 8.6% for phenytoin, −2.7% to 3.1% for phenobarbital, −2.7% to 0.5% for primidone, −8.6% to 0.3% for carbamazepine, −5.6% to 2.0% for ethosuximide, and −7.2% to 0.1% for valproate. Intralaboratory sources of imprecision significantly exceeded interlaboratory sources for many drug/method combinations. The mean CVs for intra- and interlaboratory errors for the different drugs were 6.3–7.8% and 3.3–4.2%, respectively.

Conclusions: For these long-established and relatively high-concentration analytes, the closed analytical platforms generally performed no better than open systems or chromatography, where use of calibrators prepared in house predominated. To improve the accuracy of measurements, work is required principally by the manufacturers of immunoassays to ensure minimal calibration error and to eliminate batch-to-batch variability of reagents. Individual laboratories should concentrate on minimizing dispensing errors.
LanguageEnglish
Pages1963-1969
Number of pages7
JournalClinical Chemistry
Volume48
Issue number11
Publication statusPublished - Nov 2002

Fingerprint

Anticonvulsants
Standardization
Assays
Ethosuximide
Primidone
Carbamazepine
Valproic Acid
Phenytoin
Phenobarbital
Pharmaceutical Preparations
Serum
Open systems
Chromatography
Gas chromatography
Drug Combinations
Immunoassay
Gas Chromatography
Calibration
High Pressure Liquid Chromatography

Keywords

  • accuracy
  • precision
  • measurement
  • anticonvulsants phenytoin
  • phenobarbital
  • primidone
  • carbamazepine
  • ethosuximide
  • valproate

Cite this

Wilson, J. F., Watson, I. D., Williams, J., Toseland, P. A., Thomson, A. H., Sweeney, G., ... Capps, N. E. (2002). Primary standardization of assays for anticonvulsant drugs: comparison of accuracy and precision. Clinical Chemistry, 48(11), 1963-1969.
Wilson, J.F. ; Watson, I.D. ; Williams, J. ; Toseland, P.A. ; Thomson, A.H. ; Sweeney, G. ; Smith, B.L. ; Sandle, L.N. ; Ramsey, J.D. ; Capps, N.E. / Primary standardization of assays for anticonvulsant drugs : comparison of accuracy and precision. In: Clinical Chemistry. 2002 ; Vol. 48, No. 11. pp. 1963-1969.
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Wilson, JF, Watson, ID, Williams, J, Toseland, PA, Thomson, AH, Sweeney, G, Smith, BL, Sandle, LN, Ramsey, JD & Capps, NE 2002, 'Primary standardization of assays for anticonvulsant drugs: comparison of accuracy and precision' Clinical Chemistry, vol. 48, no. 11, pp. 1963-1969.

Primary standardization of assays for anticonvulsant drugs : comparison of accuracy and precision. / Wilson, J.F.; Watson, I.D.; Williams, J.; Toseland, P.A.; Thomson, A.H.; Sweeney, G.; Smith, B.L.; Sandle, L.N.; Ramsey, J.D.; Capps, N.E.

In: Clinical Chemistry, Vol. 48, No. 11, 11.2002, p. 1963-1969.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Primary standardization of assays for anticonvulsant drugs

T2 - Clinical Chemistry

AU - Wilson, J.F.

AU - Watson, I.D.

AU - Williams, J.

AU - Toseland, P.A.

AU - Thomson, A.H.

AU - Sweeney, G.

AU - Smith, B.L.

AU - Sandle, L.N.

AU - Ramsey, J.D.

AU - Capps, N.E.

PY - 2002/11

Y1 - 2002/11

N2 - Background: The accuracy and precision of methods for the measurement of the anticonvulsants phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide, and valproate in human serum were assessed in 297 laboratories that were participants in the United Kingdom National External Quality Assessment Scheme (UKNEQAS). Methods: We distributed lyophilized, serum-based materials containing low, medium, and high weighed-in concentrations of the drugs. The 297 participating laboratories received the materials on two occasions, 7 months apart. Expected concentrations were determined by gas chromatography or HPLC methods in five laboratories using serum-based NIST reference materials as calibrators. Results: In general, bias was consistent across concentrations for a method but often differed in magnitude for different drugs. Bias ranged from −1.9% to 8.6% for phenytoin, −2.7% to 3.1% for phenobarbital, −2.7% to 0.5% for primidone, −8.6% to 0.3% for carbamazepine, −5.6% to 2.0% for ethosuximide, and −7.2% to 0.1% for valproate. Intralaboratory sources of imprecision significantly exceeded interlaboratory sources for many drug/method combinations. The mean CVs for intra- and interlaboratory errors for the different drugs were 6.3–7.8% and 3.3–4.2%, respectively. Conclusions: For these long-established and relatively high-concentration analytes, the closed analytical platforms generally performed no better than open systems or chromatography, where use of calibrators prepared in house predominated. To improve the accuracy of measurements, work is required principally by the manufacturers of immunoassays to ensure minimal calibration error and to eliminate batch-to-batch variability of reagents. Individual laboratories should concentrate on minimizing dispensing errors.

AB - Background: The accuracy and precision of methods for the measurement of the anticonvulsants phenytoin, phenobarbital, primidone, carbamazepine, ethosuximide, and valproate in human serum were assessed in 297 laboratories that were participants in the United Kingdom National External Quality Assessment Scheme (UKNEQAS). Methods: We distributed lyophilized, serum-based materials containing low, medium, and high weighed-in concentrations of the drugs. The 297 participating laboratories received the materials on two occasions, 7 months apart. Expected concentrations were determined by gas chromatography or HPLC methods in five laboratories using serum-based NIST reference materials as calibrators. Results: In general, bias was consistent across concentrations for a method but often differed in magnitude for different drugs. Bias ranged from −1.9% to 8.6% for phenytoin, −2.7% to 3.1% for phenobarbital, −2.7% to 0.5% for primidone, −8.6% to 0.3% for carbamazepine, −5.6% to 2.0% for ethosuximide, and −7.2% to 0.1% for valproate. Intralaboratory sources of imprecision significantly exceeded interlaboratory sources for many drug/method combinations. The mean CVs for intra- and interlaboratory errors for the different drugs were 6.3–7.8% and 3.3–4.2%, respectively. Conclusions: For these long-established and relatively high-concentration analytes, the closed analytical platforms generally performed no better than open systems or chromatography, where use of calibrators prepared in house predominated. To improve the accuracy of measurements, work is required principally by the manufacturers of immunoassays to ensure minimal calibration error and to eliminate batch-to-batch variability of reagents. Individual laboratories should concentrate on minimizing dispensing errors.

KW - accuracy

KW - precision

KW - measurement

KW - anticonvulsants phenytoin

KW - phenobarbital

KW - primidone

KW - carbamazepine

KW - ethosuximide

KW - valproate

UR - http://www.clinchem.org/content/48/11/1963.abstract

M3 - Article

VL - 48

SP - 1963

EP - 1969

JO - Clinical Chemistry

JF - Clinical Chemistry

SN - 0009-9147

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Wilson JF, Watson ID, Williams J, Toseland PA, Thomson AH, Sweeney G et al. Primary standardization of assays for anticonvulsant drugs: comparison of accuracy and precision. Clinical Chemistry. 2002 Nov;48(11):1963-1969.