Rapid quantitative analysis of ormeloxifene and its active metabolite, 7-desmethyl ormeloxifene, in rat plasma using liquid chromatography-tandem mass spectrometry

摘要

Ormeloxifene (ORM) is a non-steroidal, selective estrogen receptor modulator used as a once a week oral contraceptive and is intended for long-term clinical use by females. Therefore, a simple, sensitive and rapid LC-MS/MS method was developed and validated for simultaneous quantification of ORM and its active metabolite (7-desmethyl ormeloxifene, 7-DMO) in rat plasma. Also, the method was partially validated in human plasma. Chromatographic separation was achieved on Discovery HS C-18 column (5 mu m, 50 x 4.6 mm) with mobile phase [acetonitrile: aqueous ammonium acetate (0.01 M) buffer (85:15, %v/v)] at a flow rate of 0.8 mL/min. The calibration curve was linear (r >= 0.99) for a concentration range of 0.78-100 ng/mL for both the analytes. The precision (%RSD; ORM, 1.3 to 13.4; 7-DMO, 3.1 to 15.0) and accuracy (%bias; ORM, -13.8 to 12.5; 7-DMO, -10.6 to 6.8) in both rat and human plasma were within the acceptable limits. The recovery for ORM and 7-DMO was always >79.1% and >72.9%, respectively. Both the analytes were found stable in rat plasma even after 30 days of storage at -80 degrees C and on being subjected to three freeze thaw cycles. The method has not only short run time (3.5 min) but requires a low plasma sample volume (20 mu L) and is the first reported LC-MS/MS method for simultaneous quantification of the marketed drug known as centchroman (INN: ormeloxifene) and the metabolite 7-DMO in plasma. The method was applied to evaluate drug-drug interaction of ORM with the commonly prescribed antidepressant drug sertraline using serial sampling in rats. (C) 2015 Elsevier B.V. All rights reserved.