Determination of a highly selective mixed-affinity sigma receptor ligand, in rat plasma by ultra performance liquid chromatography mass spectrometry and its application to a pharmacokinetic study

作者：Jamalapuram Seshulatha; Vuppala Pradeep K; Mesangeau Christophe; McCurdy Christopher R; Avery Bonnie A^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2012, 891: 1-6.

DOI：10.1016/j.jchromb.2011.12.013

• Sigma receptor ligand
• UPLC/MS
• Method validation
• Pharmacokinetics

A selective, rapid and sensitive ultra performance liquid chromatography mass spectrometry (UPLC/MS) method was developed and validated to quantitate a highly selective mixed-affinity sigma receptor ligand, CM156 (3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo[d] thiazole-2(3H)-thione), in rat plasma. CM156 and the internal standard (aripiprazole) were extracted from plasma samples by a single step liquid-liquid extraction using chloroform. The analysis was carried out on an ACQUITY UPLC (TM) BEH HILIC column (1.7 mu m, 2.1 mm x 50 mm) with isocratic elution at flow rate of 0.2 mL/min using 10 mM ammonium formate in 0.1% formic acid and acetonitrile (10:90) as the mobile phase. The detection of the analyte was performed on a mass spectrometer operated in selected ion recording (SIR) mode with positive electrospray ionization (ESI). The validated analytical method resulted in a run time of 4 min and the retention times observed were 2.6 +/- 0.1 and 2.1 +/- 0.1 min for CM156 and the IS, respectively. The calibration curve exhibited excellent linearity over a concentration range of 5-4000 ng/mL with the lower limit of quantification of 5 ng/mL. The intra- and inter-day precision values were below 15% and accuracy ranged from -6.5% to 5.0%. The mean recovery of CM156 from plasma was 96.8%. The validated method was applied to a pilot intravenous pharmacokinetic study in rats.

• 出版日期2012-4-1