Biomolecules & Therapeutics

The Korean Society of Applied Pharmacology (한국응용약물학회)
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Simplified HPLC Method for the Determination of Mirtazapine in Human Plasma and Its Application to Single-dose Pharmacokinetics

  • Gwak Hye-Sun (College of Pharmacy, Ewha Womans University) ;
  • Lee Na-Young (College of Pharmacy, Dongduk Womens University) ;
  • Chun In-Koo (College of Pharmacy, Dongduk Womens University)
  • Published : 2006.03.01
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Abstract

Mirtazapine is an antidepressant agent with dual action on both the noradrenergic and serotonergic neurotransmitter systems. A simple high performance liquid chromatographic method has been developed and validated for the quantitative determination of mirtazapine in human plasma. A reversed-phase Cl8 column was used for the determination of mirtazapine with a mobile phase composed of 0.01M ammonium acetate solution (pH 4.2) and acetonitrile (75:25, v/v%) at a flow rate of 1.2 mL/min. Terazosin hydrochloride was used as an internal standard. The fluorescence detector was set at excitation and emission wavelengths of 290 and 350 nm, respectively. Intra- and inter-day precision and accuracy were acceptable for all quality control samples including the lower limit of quantification of 3 ng/mL. Mirtazapine was stable in human plasma under various storage conditions. This method was used successfully for a pharmacokinetic study using plasma samples after oral administration of a single 30 mg dose as mirtazapine base to 8 healthy volunteers. The maximum plasma concentration of mirtazapine was $64.1{\pm}28.0ng/mL$ at 1.8 h, and the area under the curve and elimination half-life were calculated to be $674.1{\pm}218.5ng\;h/mL\;and\;23.4{\pm}3.8h$, respectively.

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References

  1. Benkert, O., Muller, M. and Szegedi, A. (2002). An overview of the clinical efficacy of mirtazapine. Hum. Psychopharmacol. 17, S23-S26 https://doi.org/10.1002/hup.397
  2. Bremner, J.D. (1995). A double-blind comparison of Org 3770, amitriptyline and placebo in major depression. J. Clin. Psychiatry. 56, 519-525
  3. De Boer, T., Nefkens, F. and van Helvoirt, A. (1994). The alpha 2-adrenoceptor antagonist Org 3770 enhances serotonin transmission in vivo. Eur. J. Pharmacol. 253, R5-6 https://doi.org/10.1016/0014-2999(94)90778-1
  4. Food and Drug Administration, Guidance for Industry: Bioanalytical method validation, Center for Drug Evaluation and Research, Rockville, MD, 200l
  5. Halakis, J.A. (1995). Org 3770 (mirtazapine) vs. trazodone: a placebo controlled trial in depressed elderly patients. Hum. Psychopharmacol. 10, S125-S133 https://doi.org/10.1002/hup.470100807
  6. Kamas, H.T., Shiu, G. and Shah, V.P. (1991). Validation of bioanalytical methods. Pharm. Res. 8, 421-426 https://doi.org/10.1023/A:1015882607690
  7. Marttila, M., Jaaskelainen, J., Jarvi, R. (1995). A double-blind study comparing the efficacy and tolerability of mirtazapine and doxepine in patients with major depression. Eur. Neuropsychopharmacol. 5, 441-446 https://doi.org/10.1016/0924-977X(95)00016-I
  8. Maris, F.A., Dingler, E. and Niehues, S. (1999). High-performance liquid chromatographic saay with fluorescence detection for the routine monitoring of the antidepressant mirtazapine and its demthyl metabolite in human plasma. J. Chromatogr. B 721, 309-316
  9. Mullin, J., Lodge, A. and Bennie, E. (1996). A multicenter, double- blind, amitriptyline-controlled study of mirtazapine in patients with major depression. J. Psychopharmacol. 10, 235-240 https://doi.org/10.1177/026988119601000310
  10. Richou, H., Ruirny, P. and Charbaut, J. (1995). A multicenter, double- blind, clomipramine-controlled efficacy and safety study of Org 3770. Hum. Psychopharmacol. 10, 263-271 https://doi.org/10.1002/hup.470100403
  11. Smith, W.T., Glaudin, V., Panagides, J. and Gilvary, E. (1990). Mirtazapine vs. amitriptyline vs. placebo in the treatment of major depressive disorder. Psychopharmacol. Bull. 26, 191- 196
  12. Paanakker, J.E. and Van Hal, H.J.M. (1987). Capillary gas chromatographic assay for the routine monitoring of the antidepressant mepirzepine in human plasma. J. Chromatogr. 417, 203-207 https://doi.org/10.1016/0378-4347(87)80109-3
  13. Timmer, C.J., Paanakker, J.E. and Vries, M.V. (1997). Mirtazapine phannacokinetics with two dosage regimens and two pharmaceutical formulations. Pharm. Res. 14,98-102 https://doi.org/10.1023/A:1012067703764
  14. Zivkov, M. and de Jongh, G. (1995). Org 3770 vs. amitriptyline: a 6-week randomized double-blind multicenter trial in hospitalized patients. Hum. Psychopharmacol. 10, 173-180 https://doi.org/10.1002/hup.470100302
  15. Zivkov, M., Roes, K.C.B. and Polis, A.G. (1995). Efficacy of Org 3770 (mirtazapine) vs. amitriptyline in patients with major depressive disorder: a meta-analysis. Hum. Psychopharmacol. 10, S135-S145 https://doi.org/10.1002/hup.470100808