Journal of Pharmaceutical Investigation

The Korean Society of Pharmaceutical Sciences and Technology (한국약제학회)
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Determination of Clotiazepam in the Plasma Using Gas Chromatography/Mass Spectrometry with an Ion-Trap Detector and its Application to Pharmacokinetics in Healthy Volunteers

  • Kwon, Oh-Seung (Toxicology Lab., Korea Institute of Science and Technology) ;
  • Kim, Seung-Yong (Toxicology Lab., Korea Institute of Science and Technology) ;
  • Chung, Youn-Bok (National Research Lab. (NRL) of PK/PD, Biotechnology Research Institute, College of Pharmacy, Chungbuk National University)
  • Published : 2006.04.20
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Abstract

A method determining the plasma concentration of clotiazepam was developed by using gas chromatography/mass spectrometry with an ion-trap detector and was validated for applying pharmacokinetics to human volunteers orally taken 5 mg dose of clotiazepam. The detection limit was 1 ng/ml and the limit of quantitation was 5 ng/mt. Intraday reproducibility and accuracy bias % were less than 8.2 and 10.2% with inter-day variations for those being within 7.0 and 13.8%, respectively. The recovery of clotiazepam was higher than 87%. The principal pharmacokinetic parameters were determined from the plasma concentration-time plot by non-compartmental or two-compartmental analysis. In non-compartmental analysis, the elimination half-life of 10.4 hr and the area under the curve of 651.3 ng hr/ml were determined, and the maximal concentration (158.6 ng/ml) in the plasma was obtained at 0.56 hr post-dose. The developed method can be appropriate to apply pharmacokinetics and bioequivalence of clotiazepam.

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References

  1. C. Bellantuono, V. Reggi, G Tognani and S. Garattini, Benzodiazepines: clinical pharmacology and therapeutic use. Drugs, 19, 195-219 (1980) https://doi.org/10.2165/00003495-198019030-00004
  2. C.R. Gardner, Functional in vitro correlates of the benzodiazepine agonist-inverse agonist continuum. Prog. Neurobiol., 31, 425-476 (1988) https://doi.org/10.1016/0301-0082(88)90011-1
  3. P. Pole, Electrophysiology of benzodiazepine receptor ligands: multiple mechanisms and sites of action. Prog. Neurobiol., 31, 349-423 (1988) https://doi.org/10.1016/0301-0082(88)90014-7
  4. Y. Gaillard, J.P. Gay-Montchamp and M. Ollagnier, Simultaneous screening and quantitation of alpidem, Zolpidem, buspirone and benzodiazepines by dual-channel gas chromatography using electron-capture and nitrogen-phosphorus detection after solid-phase extraction. J. Chromatogr., 622, 197-208 (1993) https://doi.org/10.1016/0378-4347(93)80266-7
  5. R. Arendt, H.R. Ochs and DJ. Greenblatt, Electron capture GLC analysis of the thienodiazepine clotiazepam. Preliminary pharmacokinetic studies. Arzneimittelforschung, 32, 453-455 (1982)
  6. M. Shimamine, T. Masunari and Y. Nakahara, Studies on the identification of psychotropic substances. IX. Preparation and various analytical data of reference standard of new psychotropic substances, N-ethyl methylenenedioxyamphetamine, N-hydroxy methylenenedioxyamphetamine, mecloqualone, 4-methylaminorex. Phendimertrazine and phenmetrazine. Eisei Shikenjo Hokoku, 111, 47-56 (1993)
  7. M. Busch, W. Ritter and H. Mohrie, Thin-layer densitometric determination of clotiazepam in tablets and blood plasma. Arzneimittelforschung, 35, 547-551 (1985)
  8. H. Maurer and K. Pfleger, Identification and differentiation of alkylamine antihistamines and their metabolites in urine by computerized gas-chromatography-mass spectrometry. J. Chromatogr., 422, 85-101 (1987) https://doi.org/10.1016/0378-4347(87)80442-5
  9. S.Pirnay, I. Ricordel, D. Libong and S. Bouchonnet, Sensitive method for the detection of 22 benzodiazepines by gas chromatography-ion trap tandem mass spectrometry. J. Chromatogr A, 954, 235-245 (2002) https://doi.org/10.1016/S0021-9673(02)00190-5
  10. H.R. Ochs, D.J. Greenblatt and M. Knuchel, Effect of cirrhosis and renal failure on the kinetics of clotiazepam. Eur. J. Clin. Pharmacol., 30, 89-92 (1986) https://doi.org/10.1007/BF00614202
  11. Y.J. Lee, J.H. Choi, S.H. Song, C.H. Song, C.H. Seo, D.S. Kim, I.S. Park, K.S. Choi, H.K. Na, S.J. Chung, M.H. Lee and C.K. Shim, Development of K-BE test, a computer program for the analysis of bioequivalence. J. Kor. Pharm. Sci., 28, 223-229 (1998)
  12. R. Pocci, V. Dixit and V.M. Dixit, Solid-phase extraction and GC/MS confirmation of barbiturates from human urine. J. Anal. Toxicol. 16, 45-47 (1992) https://doi.org/10.1093/jat/16.1.45
  13. A.H. Wu, T.A. Onigbinde, S.S. Wong and K.G Johnson, Evaluation of full-scanning GC/ion trap MS analysis of NIDA drug-of-abuse urine testing in urine. J. Anal. Toxicol., 16, 137-141 (1992) https://doi.org/10.1093/jat/16.2.137
  14. D. de Bore, E.G de Jong and R.A. Maes, Mass spectrometric characterization of different norandrosterone derivatives by low-cost mass spectrometric detectors using electron ionization and chemical ionization. Rapid Commun. Mass Spectrom., 4, 181-185 (1990) https://doi.org/10.1002/rcm.1290040604
  15. A.Vermoesen, J. Vercammen, C. Sanders, D. Courtheyn and H.F. de Brabander, Comparison of two mass-selctive detectors with special reference to the analysis of residues of anabolics. J. Chromatogr., 564, 385-391 (1991)
  16. C. Jouvel, P. Maciejewski, P. Garcia, Y. Bonnaire, S. Horning and M.-A. Popot, Detection of diazepam in horse hair samples by mass spectrometric methods. Analyst, 125, 1765-1769 (2000) https://doi.org/10.1039/b003418p
  17. S.N. Muchohi, B.R. Ogutu, C.R.J.C. Newton and GO. Kokwaro, High-performance liquid chromatographic determination of diazepam in plasma of children with severe malaria. J. Chromatogr. B, 761, 255-259 (2001) https://doi.org/10.1016/S0378-4347(01)00284-5
  18. L.M. Carvalho, A.X. Linhares and J.R. Trigo, Determination of drug levels and the effect of diazepam on the growth of necrophagus flies of forensic importance in southeastern Brazil. Forensic Science International, 120, 140-144 (2001) https://doi.org/10.1016/S0379-0738(01)00421-2
  19. A.W. Abu-Qare and M.B. Abou-Donia, Chromatographic method for the determination of diazepam, pyridostigmine bromide, and their metabolites in rat plasma and urine. J. Chromatogr. B, 754, 503-509 (2001) https://doi.org/10.1016/S0378-4347(01)00040-8