title: 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.
abstract: 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™ BEH HILIC column (1.7 μm, 2.1 mm×50 mm) with isocratic elution at flow rate of 0.2 mL/min using 10mM 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.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, The University of Mississippi, University, MS 38677, USA.
authors.forename: Seshulatha
authors.initials: S
authors.lastname: Jamalapuram
authors.forename: Pradeep K
authors.initials: PK
authors.lastname: Vuppala
authors.forename: Christophe
authors.initials: C
authors.lastname: Mesangeau
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McCurdy
authors.forename: Bonnie A
authors.initials: BA
authors.lastname: Avery
mesh_terms: D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D003042:Cocaine / Q000037:antagonists & inhibitors; D008024:Ligands; D057230:Limit of Detection; D010879:Piperazines / Q000097:blood* / Q000493:pharmacokinetics; D051381:Rats; D017480:Receptors, sigma / Q000187:drug effects; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013457:Sulfur Compounds / Q000097:blood* / Q000493:pharmacokinetics
chemical_list: C549191:3-(4-(4-cyclohexylpiperazin-1-yl)butyl)benzo(d)thiazole-2(3H)-thione; D008024:Ligands; D010879:Piperazines; D017480:Receptors, sigma; D013457:Sulfur Compounds; D003042:Cocaine