VALIDATION FOR QUANTITATIVE OF METHADONE ENANTIOMERS AND ITS MAJOR METABOLITE USING VANCOMYCIN COLUMN COUPLED WITH MASS SPECTROMETRIC DETECTION AND ITS APPLICATION TO CLINICAL SAMPLES

Authors

  • Nurfadhlina Musa Pharmacogenomic & Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia,16150 Kubang Kerian, Kelantan, Malaysia
  • Sim Hann Liang Pharmacogenomic & Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia,16150 Kubang Kerian, Kelantan, Malaysia
  • Tan Soo Choon Pharmacogenomic & Novel Therapeutics Cluster, Institute for Research in Molecular Medicine (INFORMM), Universiti Sains Malaysia,16150 Kubang Kerian, Kelantan, Malaysia
  • Rusli Ismail Centre of Excellence for Research in AIDS (CERiA), University of Malaya, Level 17, Wisma RND, Jalan Pantai Baharu, 59990, Kuala Lumpur, Malaysia

Keywords:

Methadone, Vancomycin, LCMSMS, Enantiomers

Abstract

Objective: To develop method to measure both methadone enantiomers and its major metabolite 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine (EDDP) in clinical samples

Methods: Five hundredmicroliters plasma/serum was extracted using solid phase extraction (mixed mode SPE-C8/SCX). The eluent was evaporated, reconstituted in mobile phase (95:5, 0.003% formic acid in methanol: 20 mM* ammonium formate) and injected.

Result: The recoveries of methadone enantiomers and EDDP were 97% and 89% respectively. Under this condition, methadone enantiomers were successfully separated at baseline but not EDPP. Precision of spiked plasma for intra-day and inter-day was less than five for both methadone enantiomers and less than 12 for EDDP at medium and high quality control samples. Linear relationship between peak area ratio and internal standard were obtained for methadone in the range 5-1000ng/ml, and for EDDP from 5-500ng/ml with correlation coefficients greater than 0.99. The limit of quantification was 5ng/ml.

Conclusion: The assay was used to analyse serum samples obtained from patients enrolled in a methadone maintenance treatment program.

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References

Kreek MJ, Vocci FJ, History and current status of opioid maintenance treatments:blending conference session. J Subst Abuse Treat 2002;23(2):93-105.

Donny EC, Brasser SM, Bigelow GE, Stitzer ML, Walsh SL, Methadone doses of 100 mg or greater are more effective than lower doses at suppressing heroin self-administration in opioid-dependent volunteers. J Addiction 2005;100(10):1496-509.

Eap CB, Buclin T, Baumann P, Interindividual variability of the clinical pharmacokinetics of methadone:implications for the treatment of opioid dependence. J Clin Pharmacokinet 2002;41(14):1153-93.

Leavitt SB, Shinderman M, Maxwell S, Eap CB, Paris P, When "enough" is not enough:new perspectives on optimal methadone maintenance dose. Mt Sinai J Med 2000;67(5-6):404-11.

Kristensen K, Christensen CB, Christrup LL, The mu1, mu2, delta, kappa opioid receptor binding profiles of methadone stereoisomers and morphine. J Life Sci 1995;56(2):PL45-50.

Scott CC, Robbins EB, Chen KK, Pharmacologic comparison of the optical isomers of methadon. J Pharmacol Exp Ther 1948;93(3):282-6.

Isbell H, Eisenman AJ. The addiction liability of some drugs of the methadon series. J Pharmacol Exp Ther 1948;93(3):305-13.

Eap CB, Crettol S, Rougier JS, Schlapfer J, Sintra Grilo L, Deglon JJ, et al. Stereoselective block of hERG channel by (S)-methadone and QT interval prolongation in CYP2B6 slow metabolizers. J Clin Pharmacol Ther 2007;81(5):719-28.

Foster DJ, Somogyi AA, Dyer KR, White JM, Bochner F, Steady-state pharmacokinetics of (R)-and (S)-methadone in methadone maintenance patients. Br J Clin Pharmacol 2000;50(5):427-40.

Rodriguez-Rosas ME, Medrano JG, Epstein DH, Moolchan ET, Preston KL, Wainer IW, Determination of total and free concentrations of the enantiomers of methadone and its metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine) in human plasma by enantioselective liquid chromatography with mass spectrometric detection. J Chromatogr A 2005;1073(1-2):237-48.

Etter ML, George S, Graybiel K, Eichhorst J, Lehotay DC. Determination of free and protein-bound methadone and its major metabolite EDDP:enantiomeric separation and quantitation by LC/MS/MS. J Clin Biochem 2005;38(12):1095-102.

Foster DJ, Morton EB, Heinkele G, Murdter TE, Somogyi AA. Stereoselective quantification of methadone and a d(6)-labeled isotopomer using high performance liquid chromatography-atmospheric pressure chemical ionization mass-spectrometry: application to a pharmacokinetic study in a methadone maintained subject. J Ther Drug Monit 2006;28(4):559-67.

Lee JT, Brian HE, Beesley TE. Enhanced Chiral Selectivity by Chemical Modification of Chiral Stationary Phases For Pharmaceutically Important Drugs and Drug Metabolites. Int J Symposium on Chiral Discrimination 2004.

Foster DJ, Somogyi AA, Bochner F. Methadone N-demethylation in human liver microsomes:lack of stereoselectivity and involvement of CYP3A4. Br J Clin Pharmacol 1999;47(4):403-12.

Published

31-08-2014

How to Cite

Musa, N., S. Hann Liang, T. Soo Choon, and R. Ismail. “VALIDATION FOR QUANTITATIVE OF METHADONE ENANTIOMERS AND ITS MAJOR METABOLITE USING VANCOMYCIN COLUMN COUPLED WITH MASS SPECTROMETRIC DETECTION AND ITS APPLICATION TO CLINICAL SAMPLES”. International Journal of Pharmacy and Pharmaceutical Sciences, vol. 6, no. 8, Aug. 2014, pp. 522-7, https://innovareacademics.in/journals/index.php/ijpps/article/view/1928.

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