Published:Journal of Chromatographic Science,
ISSN 0021-9665 Volume 45,
Number 2, February 2007, pp.91-96
Rapid and Sensitive Method for the Determination
of Sibutramine Active Metabolites in Human Plasma by Reversed-Phase
Liquid Chromatography–Tandem Mass Spectroscopy
Jignesh Bhatt[1,2], Bhavin Shah[1], Sandeep Kambli[1],
Gunta Subbaiah[1], Sadhana Singh[2], and Suresh Ameta[3]
[1]Torrent Research Centre, Gandhinagar-382428, Gujarat State,
India;
[2]Department of Chemistry, B.N.P.G. College, Mohanlal Sukhadia
University, Udaipur, Rajasthan State, India; and
[3]Department of Chemistry, College of science, Mohanlal Sukhadia
University, Udaipur, Rajasthan State, India
A new, rapid, and sensitive liquid chromatography–tandem
mass spectrometry method is developed and validated to quantitate
the sibutramine active metabolites mono desmethyl sibutramine
(M1) and di-desmethyl sibutramine (M2) using imipramine as the
internal standard in human plasma samples for routine bioequivalence
studies. The method involves rapid solid-phase extraction from
plasma, eliminating the drying and reconstitution steps. The analytes
are chromatographed on a C8 reversed-phase chromatographic column
and analyzed by mass spectrometry in the multiple reaction monitoring
mode, which enables a quantitation limit at the sub-nanogram level.
The method has a chromatographic run time of 2.8 min. The proposed
method is validated with a linear range of 0.1–8.0 and 0.2–16.0
ng/mL for M1 and M2, respectively, with a correlation coefficient
of regression ≥ 0.9990. The method is sensitive and reproducible,
having intra- and inter-assay precision at the lower limit of
quantitation (0.1 ng/mL for M1 and 0.2 ng/mL for M2) < 10.0%.
The overall recovery for M1 and M2 is 93.5% and 77.9%, respectively.
The method has been applied to a bioequivalence clinical study
with great success.
Reproduction
of editorial content of this journal is prohibited without publisher’s
permission.
This
article is available in its entirety by fax for $40.00.
Visa, MasterCard & Amex accepted.
To
order electronicallyclick here or call: 847-647-2900 ext. 1323 or fax request to: 847-647-1155.
Please
indicate JCS volume and issue along with
page numbers.
For permission to reuse material from Journal of Chromatographic Science, please access www.copyright.com or contact the Copyright Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. CCC is a not-for-profit organization that provides licenses and registration for a variety of uses.
