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Pharmaceutisch weekblad

, Volume 1, Issue 1, pp 1171–1204 | Cite as

Joint international quality control programme on the determination of antiepileptic drugs

  • I. C. Dijkhuis
  • H. J. De Jong
  • A. Richens
  • C. E. Pippenger
  • E. E. A. Leskinen
  • A. P. W. Nyberg
Original Articles Related to the Theme
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Abstract

In a joint effort, 4 existing Quality Control programmes organized in September 1978 a test on the determination of antiepileptic drugs and made an inventory of the various methods of analysis used.

To approx. 700 laboratories 3 lyophilized calf s serum specimens, each of them spiked with 8Ae drugs, were distributed together with an extensive questionnaire. The number of laboratories reporting results, were: phenobarbital 601, phenytoin 624, carbamazepine 398, 10, 11- epoxide-Cbz 15, primidone 434, ethosuximide 302, valproic acid 167 and clonazepam 26; approx. 95% of them also completed the questionnaire.

As to themethods per Q.C. programme,Emit was mainly used in USA,Glc in Europe,Hplc in USA (Rp systems) and in The Netherlands (sp systems),Ria in USA and Scandinavia.

As to theresults per method,Emit, Glc andHplc produced similar results in therapeutic and sub-toxic concentrations ofPb, Dph andPri; in the sub-therapeutic range of these drugs,Glc andHplc gave better results thanEmit (which produced values 10–20% higher than the theoretical ones).

InEsm andVal, Glc-methods are preferred while inCbz, Hplc is the method of choice, followed byEmit. InClona, severalGlc andHplc methods are still under investigation. Spectrophotometric determinations (mainly used inPb, Dph andCbz) proved to be not reliable.

In tables, results per technique are subdivided into approx. 5 methods. This enables to distinguish betweene.g.Glc-derivatization with and without previous clean up or betweenEmit-automatic < 10Μl and 50Μl samples. Per drug, the various methods of assay are discussed; also, methods and results are given when drugs were determined simultaneously. Bovine serum (calfs serum) proved to be a suitable matrix in all methods used.

Keywords

Carbamazepine Valproic Acid Phenobarbital Clonazepam Primidone 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Abbreviations and symbols

Apparatus and analytical techniques

AFID

alkaliflame ionization detection or nitrogen detection,used in GLC

ECD

electron capture detection,used in GLC

EMIT

enzyme multiplied immunoassay technique

FID

flame ionization detection,used in GLC

GLC

gas liquid chromatography

HPLC

high pressure liquid chromatography

RP

reversed phase,used in HPLC

RIA

radioimmunoassay

SP

straight (or normal) phase,used in HPLC

TLC

thin layer chromatography

Drugs, internal standards, reagents

A.E.

(D) antiepileptic (drugs)

CBZ

carbamazepine

CLONA

clonazepam

DCM

dichloromethane

DMMS

α,α-dimethyl-Β-methylsuccinimide,int. stand. for ESM

DPH

phenytoin, 5,5-diphenylhydantoin

ep. CBZ

10,11-epoxide-carbamazepine,metabolite of CBZ

ESM

ethosuximide

int. stand.

internal standard

MPB

5-methylphenobarbital, 5-ethyl-5(p.methylphenyl) barbituric acid,int. stand, for PB

MPPH

-5-(p.methylphenyl)5-phenylhydantoin,int. stand, for DPH

MPD

4-methylprimidone,int. stand, for PRI

MPS

α-methyl-α-propylsuccinimide,int. stand, for ESM

NA

naphthenic acid, cyclohexane carboxylic acid,int. stand, for VAL

PB

phenobarbital

PRI

primidone

TMAH

tetramethylammonium hydroxide

TMPAH

trimethylphenylammonium hydroxide

VAL

valproic acid, dipropylacetic acid

Miscellaneous

Barts

Bartholomew's Hospital, Quality Control

BP

(1973) British Pharmacopoeia (1973)

cl. up

clean up

diss.

dissolution

evap.

evaporation

N

number of results, tests, laboratories etc.

NT

total number of N

NR

number of rejected N (deviation from ¯x is > 3 sd)

Q.C.

quality control

Rt

retention time

SD

standard deviation

temp.

temperature (in ‡C)

VC

coefficient of variation

¯x

mean value

¯x, (%)

mean value in percentages relative to the weighed-in value

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References

  1. Adams, R. G., andF. L. Vandenmark (1976) SimultaneousHplc determination of some anticonvulsants in serum,Clin Chem. 22, 25–31.PubMedGoogle Scholar
  2. Beer, P. De, andI. C. Dijkhuis (1976) Bepaljng van carbamazepine in serum: vergelijkend onderzoek naar de mogelijkheden van enkele methoden,Pharm. Weekblad 111, 93–102.Google Scholar
  3. Berlin, A., S. Agurell, O. Borgä, L. Lund andF. Sjöqvist (1972) Micromethod for the determination of diphenylhydantoine in plasma and cerebrospinal fluid: a comparison between aGlc and a spectrophotometric method,Scand. J. Clin. Lab Invest. 29, 281–287.CrossRefPubMedGoogle Scholar
  4. Bius, D. L., H. J. Kupferberg andK. H. Dudley (1978) Carbamazepine: Determination by silylation, in:Pippenger et al. (1978b) 347.Google Scholar
  5. Booker, H. E., andB. A. Darcey (1978a) Phenobarbital, Primidone and Phenytoin. Simultaneous determination without derivatization, in:Pippenger et al (1978b) blz. 342–344; (1978b) Carbamazepine. Determination without derivatization, in:Pippenger et al. (1978b) 345–347; (1978c) Ethosuximide. Determination without derivatization, in:Pippenger et al. (1978b) 349–350.Google Scholar
  6. Buchanan, R. A., L. Fernandez andA. W. Kinkel (1969) Absorption and elimination of ethosuximide in children,J. Clin. Pharmacol. 9, 393–398.Google Scholar
  7. Christiansen, J. (1971) Assay of drugs and metabolites in capillary blood,Scand. J. Clin. Lab. Invest. 27, Suppl. 118, 67.Google Scholar
  8. Dill, W. A., L. Chucot, T. Chang andA. J. Glazko (1971) Simplified benzophenone procedure for the determination of diphenylhydantoin in plasma,Clin. Chem. 17, 1200.PubMedGoogle Scholar
  9. Dudley, K. H., D. L. Bius, B. S. Kraus andL. W. Boyles (1975) in:Pippenger et al. (1978b) 35–41.Google Scholar
  10. Dijk, A. Van, andD. R. A. Uges (1979) Phenobarbital, Phenytoin, Primidone and Carbamazepine, in:Merkus (ed.)Serum concentrations of drugs. Exerpta Medica, Amsterdam-New York 1979.Google Scholar
  11. Dukhuis, I. C. (1975) Inter-laboratoriumonderzoek naar de bepaling van anti-epileptica in plasma en serum met beh:ulp van gelyofiliseerd standaardplasma,Pharm. Weekblad 110, 1177–1199; (1979)Quality control of drug assays in therapy and toxicology. Thesis, Leiden.Google Scholar
  12. Dijkhuis, I. C., E. W. De Flines andJ. Rengerink (1979) Preparation of lyophilized drug spiked calf s serum,Pharm. Weekblad Sci. Ed. 1, 185–193.Google Scholar
  13. Dukhuis, I. C., andE. Vervloet (1974) Rapid determination of the antiepileptic drug di-n-propylacetic acid in serum,Pharm. Weekblad 109, 30–33.Google Scholar
  14. Friel, P., andJ. R. Green (1973) Quantitative assay for carbamazepine levels byGlc,Clin. Chim. Acta 43, 413–420.CrossRefGoogle Scholar
  15. Freeman, D. J., andN. Rawal (1979) Serum anticonvulsant monitoring byHplc with a methanolic mobile phase,Clin. Chem. 25, 810–811.PubMedGoogle Scholar
  16. Hagenaar, K. E., andH. J. De Jong (1979) Interactive computer processing of test results.Pharm. Weekblad Sci. Ed. 1, 197–198.Google Scholar
  17. Hamilton, H. E., andJ. E. Wallace (1978) Ultraviolet spectrophotometric quantitation of phenytoin and phenobarbital, in:Pippenger et al. (1978b) 175–183.Google Scholar
  18. Harvey, C. D., andA. L. Sherwin (1978)Glc quantitation of ethosuximide, in:Pippenger et al. (1978b) 87–93.Google Scholar
  19. Hundt H. K., andE. C. Clark (1975) Thin layer Chromatographie method for the determination of carbamazepine and two of its metabolites in serum:J. Chromatogr. 107, 149–154.CrossRefPubMedGoogle Scholar
  20. Kabra, P. M., andB. E. Stafford (1977) Simultaneous measurement of phenobarbital, phenytoin, primidone, ethosuximide, and carbamazepine in serum byHplc,Clin. Chem. 23, 1284.PubMedGoogle Scholar
  21. Kleijn, E. Van Der, P. Collste, B. Norlander, S. Agurell andF. Sjöqvist (1973)Glc determination of ethosuximide and phensuximide in plasma and urine of man,J. Pharm. Pharmacol. 25, 324–327.CrossRefPubMedGoogle Scholar
  22. Knop, H. L., E. Van Der Kleijn andL. C. Edmunds (1975) The determination of clonazepam in plasma byGlc,Pharm. Weekblad 110, 297–309.Google Scholar
  23. Kumps, A., andY. Mardens (1975) A rapidGlc determination of serum levels of phenobarbital and diphenylhydantoin,Clin. Chim. Acta 62, 371–376.CrossRefPubMedGoogle Scholar
  24. Kupferberg, H. J. (1970) Quantitative estimation of di-phenylhydantoin, primidone and phenobarbital in plasma byGlc,Clin. Chim, Acta 29, 283–288; (1972)Glc determination of carbamazepine in plasma,J. Pharm. Sci. 61, 284–286: (1978)Glc quantification of valproic acid, in:Pippenger et al. (1978b) 147–151.CrossRefGoogle Scholar
  25. Meilink, J. W. (1974) Fluorometric assay of carbamazepine and its metabolites in blood,Pharm. Weekblad 109, 22–30.Google Scholar
  26. Meuer, J. W. A., H. Meinardi, C. Gardner-Thorpe andE. Van Der Kleijn (1973)Methods of analysis of anti-epileptic drugs. Exerpta Medica, Amsterdam/American Elsevier Company Inc., New York.Google Scholar
  27. Perchalski, R. J. andB. J. Wilder (1974) RapidGlc determination of carbamazepine in plasma,Clin. Chem. 20, 492; (1978) Evaluation of on-column methylation inGlc-quantification of antiepileptic drugs, in:Pippenger et al. (1978b) 75–85.PubMedGoogle Scholar
  28. Pippenger, C. E., H. Paris-Kutt, J. K. Penry andD. D. Daly (1978a) Antiepileptic drug levels quality control programme: interlaboratory variability., in:Pippenger et al. (1978b) 187–197.Google Scholar
  29. Pippenger, C. E., J. K. Penry andH. Kutt (1978b)Antiepileptic Drugs: Quantitative Analysis and Interpretation. Raven Press, New York.Google Scholar
  30. Pippenger, C. E., J. K. Penry, B. G. White, D. D. Daly andR. Buddington (1976) Interlaboratory variability in determination of plasma antiepileptic drug concentrations,Arch. Neurol. 33, 351–355.CrossRefPubMedGoogle Scholar
  31. Richens, A. (1978) Drug level monitoring — Quantity and Quality,Brit. J. Clin. Pharmacol. 5, 285–288.CrossRefGoogle Scholar
  32. Roger, J. C., G. Rodgers jr. andA. Soo (1973) Simultaneous determination of carbamazepine and other anticonvulsants in human plasma byGlc,Clin. Cliem. 19, 590–592.Google Scholar
  33. Schmidt, D.,et al. (1977) Interlaboratory variability of valproic acid determinations,Arzneimittel-Forsch. 27, 1078–1081.Google Scholar
  34. Schobben, A. F. A. M., andE. Van Der Kleijn (1974) Determination of sodium di-n-propylacetate in plasma byGlc,Pharm. Weekblad 109, 30–33.Google Scholar
  35. Sichler, D. W., andC. E. Pippenger (1978) Phenobarbital, carbamazepine, primidone and phenytoin: simultaneous determination with on-column methylation (Tmpah), in:Pippenger et al. (1978b) 335–337.Google Scholar
  36. Silva, J. A. F. De, andI. Bekersky (1974) Determination of clonazepam and flunitrazepam in blood by electron captureGlc,J. Chromatogr. 99, 447–460.CrossRefPubMedGoogle Scholar
  37. Silva, J. A. F. De, I. Bekersky, C. V. Puglisi, M. A. Brooks andR. E. Weinfeld (1976) Determination of 1,4-benzodiazepines and diazepin-2-ones in blood by electron captureGlc,Anal. Chem. 48, 10–19.CrossRefPubMedGoogle Scholar
  38. Schottelius, D. D. (1978) Homogeneous Immunoassay system (Emit) for quantitation of antiepileptic drugs in biological fluids, in:Pippenger et al. (1978b) blz. 95–108.Google Scholar
  39. Soldin, S., andJ. G. Hill (1976) Rapid micromethod for measuring anticonvulsant drugs in serum byHplc,Clin. Chem. 22, 856.PubMedGoogle Scholar
  40. Uges, D. R. A., andP. Bouma (1978a) An improved determination of clonazepam in serum byHplc,Pharm. Weekblad 113, 1156–1158; (1978b)HPLC-bepaling van fenobarbital, fenytoÏne, ethosuximide, carbamazepine enCBZ-epoxide in serum,Med. Ned. Ver. Ziekenhuisapothekers 35, 320–323.Google Scholar
  41. Wallace, J. E., J. K. Farguhar, H. E. Hamilton andB. A. Everhart (1974) Comments on the determination of diphenylhydantoin,Clin. chem. 20, 515–516.PubMedGoogle Scholar
  42. Westenberg, H. G. M. (1978)Pharmacokinetics of carbamazepine. Thesis, State University Groningen.Google Scholar
  43. Westenberg, H. G. M., andR. A. De Zeeuw (1976) Rapid and sensitiveGlc determination of carbamazepine suitable for use in monitoring multiple-drug anticonvulsant therapy,J. Chromatogr. 118, 217–224.CrossRefPubMedGoogle Scholar
  44. Ijdenberg, F. N. (1975) Een alkyleringsmethode ten dienste van de gaschromatografische bepaling van antiepileptica,Pharm. Weekblad 110, 21–24.Google Scholar

Copyright information

© Bohn, Scheltema & Holkema 1979

Authors and Affiliations

  • I. C. Dijkhuis
    • 1
  • H. J. De Jong
    • 2
  • A. Richens
    • 3
  • C. E. Pippenger
    • 4
  • E. E. A. Leskinen
    • 5
  • A. P. W. Nyberg
    • 5
  1. 1.Department of Clinical Pharmacy and ToxicologyThe Hague Hospitals Central PharmacyThe HagueThe Netherlands
  2. 2.Department of Analytical Chemistry and Pharmaceutical Analysis, Gorlaeus LaboratoriesState University of LeidenLeidenThe Netherlands
  3. 3.Institute of NeurologyLondonEngland
  4. 4.Columbia University,College of Physicians & SurgeonsDepartment of NeurologyNew York
  5. 5.Department of Clinical LaboratoryKivelä HospitalHelsinkiFinland

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