Share This Article:

Development and Validation of an LC-MS/MS Method for Quantitative Analysis of Mirtazapine in Human Plasma

Abstract Full-Text HTML Download Download as PDF (Size:203KB) PP. 650-657
DOI: 10.4236/ajac.2011.26074    7,269 Downloads   14,143 Views   Citations

ABSTRACT

Mirtazapine (MTZ) is an antidepressant drug, which belongs to the chemical class of piperazinoazepines. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the quantifica- tion of MTZ in plasma at the concentrations associated with therapy. Diazepam (DZP) was used as internal standard, added to 200 μL of plasma sample prior to a liquid-liquid extraction using hexane. Chroma- tographic separation was achieved on an Agilent® Eclipse XDB C-18 column (100 × 2.1 mm, 3.5 μm) in iso- cratic mode at 40?C. Mobile phase was 10 mM ammonium acetate/acetonitrile/formic acid (60/40/0.1, v/v/v) at a constant flow rate of 0.5 mL?min–1. The injection volume was 10 ?L and the total run time was 3.2 min. The method shows selectivity and linearity. The detection and quantitation limits were established at 0.17 and 0.50 ng?mL–1, respectively. The extraction recoveries for MTZ and DZP were found to be between 84.9 and 93.9%. The intra-day and inter-day precision and accuracy fulfill at the international acceptance criteria. The method shows to be stable for the studied parameters. Therefore, a rapid, specific, and sensitive LC-MS/MS method for quantification of MTZ in human plasma was developed and can be used in therapeu- tic drug monitoring of this drug.

Conflicts of Interest

The authors declare no conflicts of interest.

Cite this paper

M. Chorilli, R. Bonfilio, C. Louvandini, F. Gonçalves and H. Salgado, "Development and Validation of an LC-MS/MS Method for Quantitative Analysis of Mirtazapine in Human Plasma," American Journal of Analytical Chemistry, Vol. 2 No. 6, 2011, pp. 650-657. doi: 10.4236/ajac.2011.26074.

References

[1] J. Fawcett and R. L. Barkin, “Review of the Results from Clinical Studies on the Efficacy, Safety and Tolerability of Mirtazapine for the Treatment of Patients with Major De-pression,” Journal of Affective Disorders, Vol. 51, No. 3, 1998, pp. 267-285. doi:10.1016/S0165-0327(98)00224-9
[2] S. A. K. Anttila and E. V. J. Leinonen, “A Review of the Pharmacological and Clinical Profile of Mirtazapine,” CNS Drug Reviews, Vol. 7, No. 3, 2001, pp. 249-264. doi:10.1111/j.1527-3458.2001.tb00198.x
[3] J. M. Gorman, “Mirtazapine: A Clinical Overview,” Journal of Clinical Psychiatry, Vol. 60, No. 17, 1999, pp. 9-13.
[4] L. P. C. Delpressine, M. E. G. Moonen, F. M. Kaspersen, G. N. Wagenaars, P. L. Jacobs, C. J. Timmer, J. E. Paa-nakker, H. J. M. Van Hal and G. Voortman, “Phar- ma-cokinetics and Biotransformation of Mirtazapine in Human Volunteers,” Clinical Drug Investigation, Vol. 15, No. 1, 1998, pp. 45-55. doi:10.2165/00044011-199815010-00006
[5] C. J. Timmer, J. M. Sitsen and L. P. Delbressine, “Clini- cal Pharmacokinetics of Mirtazapine,” Clinical Pharma- cokinetics, Vol. 38, No. 6, 2000, pp. 461-474. doi:10.2165/00003088-200038060-00001
[6] L. Delbressine, M.-L. Dahl, H. M. Van den Wildenberg, H. J. Kleijn and L. Bertilsson, “In Vivo Study in Humans on Disposition of the Enantiomers and Metabolites of Mirtazapine,” European Neuropsychopharmacology, Vol. 7, No. 2, 1997, pp. 145-145. doi:10.1016/S0924-977X(97)88483-0
[7] S. Budavari, M. J. O’Neil, A. Smith and P. E. Heckelman, “The Merck Index, an Encyclopedia of Chemicals, Drugs, and Biologicals,” 11th Edition, Merck & Co, Whitehouse Station, 2001.
[8] J. E. Paanakker and H. J. M. Van Hal, “Capillary Gas Chromatographic Assay for the Routine Monitoring of the Antidepressant Mepirzepine in Human Plasma,” Journal of Chromatography B, Vol. 417, No. 1, 1987, pp. 203-207.
[9] S. R. Kuchekar, M. L. Kundlik and B. H. Zaware, “Rapid Quantification of Mirtazapine and Desmethyl Mirtazapine in Human Plasma by LC-ESI-MS/MS: Application to a Bioequivalence Study,” Journal of Saudi Chemical Soci- ety, Vol. 15, No. 2, 2011, pp. 145-153. doi:10.1016/j.jscs.2010.07.001
[10] P. J. Taylor, “Matrix Effects: The Achilles Heel of Quan- titative High-Performance Liquid Chromatography-Elec- trospray-Tandem Mass Spectrometry,” Clinical Bio- chemistry, Vol. 38, No. 4, 2005, pp. 328-334. doi:10.1016/j.clinbiochem.2004.11.007
[11] R. N. Xu, L. Fan, M. J. Rieser and T. A. El-Shourbagy, “Recent Advances in High-Throughput Quantitative Bioanalysis by LC–MS/MS,” Journal of Pharmaceutical and Biomedical Analysis, Vol. 44, No. 2, 2007, pp. 342-355. doi:10.1016/j.jpba.2007.02.006
[12] FDA, “Guidance for Industry, Bioanalytical Method Va-lidation,” 2001. http://www.fda.gov/downloads/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm070107.pdf
[13] K. Jinno, M. Taniguchi and M. Hayashida, “Solid Phase Micro Extraction Coupled with Semi-Microcolumn High Performance Liquid Chromatography for the Analysis of Benzodiazepines in Human Urine,” Journal of Pharma- ceutical and Biomedical Analysis, Vol. 17, No. 6-7, 1998, pp. 1081-1091. doi:10.1016/S0731-7085(98)00074-0
[14] M. H. de Oliveira, M. E. C. Queiroz, D. Carvalho, S. M. Silva and F. M. Lan?as, “Determination of Diazepam in Human Plasma by Solid-Phase Microextraction and Cap- illary Gas Chromatography-Mass Spectrometry,” Chro- matographia, Vol. 62, No. 3-4, 2005, pp. 215-219. doi:10.1365/s10337-005-0601-0
[15] V. P. Shah, K. K. Midha, S. Dighe, I. McGilvery, J. P. Skelly, A. Yakobi, T. Layloff, C. T. Viswanathan, C. E. Cook, R. D. McDowall, K. A. Pittman and S. Spector, “Analytical Methods Validation: Bioavailability, Bio- equivalence, and Pharmacokinetic Studies,” Pharmaceu- tical Research, Vol. 9, No. 4, 1992, pp. 588-592. doi:10.1023/A:1015829422034
[16] L. Du, D. G. Musson and A. Q. Wang, “Stability Studies of Vorinostat and Its Two Metabolites in Human Plasma, Serum and Urine,” Journal of Pharmaceutical and Bio- medical Analysis, Vol. 42, No. 5, 2006, pp. 556-564. doi:10.1016/j.jpba.2006.05.005
[17] FDA, “Guideline for Submitting Samples and Analytical Data for Method Validations,” 1987. http://www.fda.gov/Drugs/GuidanceComplianceRegulatoryInformation/Guidances/ucm123124.htm

  
comments powered by Disqus

Copyright © 2020 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.