Stereoselective High-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Determination of R- and S-Acenocoumarol in Human Plasma and Its Application in a Pharmacokinetics Study

Abstract

A stereoselective, sensitive and rapid liquid chromatography-tandem mass spectrometry (LC-MSMS) method for the determination of R-acenocoumarol and S-acenocoumarol in human plasma was developed and validated at IPRC bioanalytical labs. The procedure involved solid phase extraction of both enantiomers and their corresponding internal standard. The chromatographic separation was accomplished employing a chiral column and proper mobile phase. Detection was carried out using Waters Micromass® Quattro Premier mass spectrometer in multiple reaction monitoring (MRM) mode using turbo ion spray with negative ionization. The method was validated over a linear range of 0.40 - 40.00 ng/ml for R-acenocoumarol and 0.20 - 20.00 ng/ml for the S-acenocoumarol. Method validation covered different parameters such as linearity, accuracy, precision and stability. The method was successfully applied for the determination of R and S-acenocoumarol in plasma samples of 28 healthy subjects who participated in a pharmacokinetics study.

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Salem, I. , Abdullah, M. and Najib, N. (2015) Stereoselective High-Performance Liquid Chromatography Tandem Mass Spectrometry Method for Determination of R- and S-Acenocoumarol in Human Plasma and Its Application in a Pharmacokinetics Study. American Journal of Analytical Chemistry, 6, 216-227. doi: 10.4236/ajac.2015.63020.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] Hirsh, J., Dalen, J.E., Anderson, D.R., Poller, L., Bussey, H., Ansell, J., Deykin, D. and Brandt, J.T. (1998) Oral Anti-coagulants: Mechanism of Action, Clinical Effectiveness, and Optimal Therapeutic Range. Chest, 114, 445S-469S.
http://dx.doi.org/10.1378/chest.114.5_Supplement.445S
[2] Hirsh, J., O’Donnell, M. and Weitz, J.I. (2005) New Anticoagulants. Blood, 105, 453-463.
http://dx.doi.org/10.1182/blood-2003-12-4195
[3] Weitz, J.I. (2004) New Anticoagulants for Treatment of Venous Thrombo-Embolism. Circulation, 110, I19-I26.
http://dx.doi.org/10.1161/01.CIR.0000140901.04538.ae
[4] Saraeva, R.B., Paskaleva, I.D., Doncheva, E., Eap, C.B. and Ganev, V.S. (2007) Pharmacogenetics of Acenocoumarol: CYP2C9, CYP2C19, CYP1A2, CYP3A4, CYP3A5 and ABCB1 Gene Polymorphisms and Dose Requirements. Journal of Clinical Pharmacy and Therapeutics, 32, 641-649.
http://dx.doi.org/10.1111/j.1365-2710.2007.00870.x
[5] Thijssen, H.H., Baars, L.G. and Reijnders, M.J. (1983) Analysis of Acenocoumarin and Its Amino and Acetamido Metabolites in Body Fluids by High-Performance Liquid Chromatography. Journal of Chromatography B, 274, 231-238.
http://dx.doi.org/10.1016/S0378-4347(00)84426-6
[6] Thijssen, H.H., Janssen, G.M. and Baars, L.G. (1986) Lack of Effect of Cimetidine on Pharmacodynamics and Kinetics of Single Oral Doses of R- and S-Acenocoumarol. European Journal of Clinical Pharmacology, 30, 619-623.
http://dx.doi.org/10.1007/BF00542424
[7] Thijssen, H.H., Drittij, M.J., Vervoort, L.M. and de Vries-Hanje, J.C. (2001) Altered Pharmacokinetics of R- and S-Acenocoumarol in a Subject Heterozygous for CYP2C9*3. Clinical Pharmacology & Therapeutics, 70, 292-298.
http://dx.doi.org/10.1067/mcp.2001.117936
[8] Vecchione, G., Casetta, B., Tomaiuolo, M., Grandone, E. and Margaglione, M. (2007) A Rapid Method for the Quantification of the Enantiomers of Warfarin, Phenprocoumon and Acenocoumarol by Two-Dimensional-Enantioselective Liquid Chromatography/Electrospray Tandem Mass Spectrometry. Journal of Chromatography B, 850, 507-514.
http://dx.doi.org/10.1016/j.jchromb.2006.12.050
[9] Kollroser, M. and Schober, C. (2002) Determination of Coumarin-Type Anticoagulants in Human Plasma by HPLC-Electrospray Ionization Tandem Mass Spectrometry with an Ion Trap Detector. Clinical Chemistry, 48, 84-91.
[10] Willoughby, R., Sheehan, E. and Mitrovich, S. (2002) A Global View of LC/MS. 2nd Edition, Global View Publishing, Pittsburgh.
[11] The European Medicines Agency (EMA) (2014) Note for Guidance on Good Clinical Practice (CPMP/ICH/135/95).
www.ema.europa.eu/
[12] World Medical Association (2000) Declaration of Helsinki. Amended by the 52nd World Medical Assembly (WMA), Edinburgh. (Note Added in Tokyo, 2004 and Updated in Seoul, 2008)
[13] US Department of Health and Human Services, Food and Drug Administration, Center for Drug Evaluation and Research (CDER) (2001) Guidance for Industry, Bioanalytical Method Validation.

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