M. CHORILLI ET AL.
656
Table 5. Standard solution stability data.
Solution stability test Mirtazapine Diazepam (IS)
Mean area CV (%) Area (%) Mean area CV (%) Area (%)
At ambient temperature (25˚C)
Initial (n = 5) 45677 3.3 100.00 41976 5.3 100.00
17 hours ( n = 5) 45684 1.3 100.02 46192 1.9 110.04
Between 2˚C and 8˚C
Initial (n = 5) 35799 3.5 100.00 31549 3.6 100.00
10 days ( n = 5) 35156 3.5 98.20 33323 3.1 105.62
developed and validated. A simple and inexpensive liq-
uid-liquid extraction procedure and an isocratic chroma-
tography condition using a reversed-phase column pro-
vided an assay well suited for real time analyses. The
method exhibited excellent performance in terms of se-
lectivity, linearity, accuracy, precision, recovery, stability,
detection limit and quantitation limit.
In addition, the reported method has a short analysis
run time, an advantage over previously reported methods.
Therefore, this method is suitable for therapeutic drug
monitoring of MTZ and can be used in pharmacokinetic
or bioequivalence studies of this drug.
5. Acknowledgements
The authors are grateful to FAPESP (São Paulo, Brazil),
CNPq (Brasília, Brazil) and PADC/FCF/UNESP (Ara-
raquara, Brazil) for research fellowships.
6. 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
Depression,” 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.
Paanakker, H. J. M. Van Hal and G. Voortman, “Phar-
macokinetics 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
Validation,” 2001.
http://www.fda.gov/downloads/Drugs/GuidanceComplian
ceRegulatoryInformation/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-
Copyright © 2011 SciRes. AJAC