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Ultra‐performance liquid chromatography tandem mass spectrometry method for the determination of AZ66, a sigma receptor ligand, in rat plasma and its application to in vivo pharmacokinetics
Author(s) -
Jamalapuram Seshulatha,
Vuppala Pradeep Kumar,
Abdelazeem Ahmed H.,
McCurdy Christopher R.,
Avery Bonnie A.
Publication year - 2013
Publication title -
biomedical chromatography
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.4
H-Index - 65
eISSN - 1099-0801
pISSN - 0269-3879
DOI - 10.1002/bmc.2901
Subject(s) - chemistry , chromatography , pharmacokinetics , mass spectrometry , high performance liquid chromatography , selected reaction monitoring , tandem mass spectrometry , liquid chromatography–mass spectrometry , triple quadrupole mass spectrometer , detection limit , sigma receptor , in vivo , analyte , metabolite , receptor , pharmacology , microbiology and biotechnology , biology , medicine , biochemistry
Methamphetamine abuse continues as a major problem in the USA owing to its powerful psychological addictive properties. AZ66, 3‐[4‐(4‐cyclohexylpiperazine‐1‐yl)pentyl]‐6‐fluorobenzo[d]thiazole‐2(3H)‐one, an optimized sigma receptor ligand, is a promising therapeutic agent against methamphetamine. To study the in vivo pharmacokinetics of this novel sigma receptor ligand in rats, a sensitive ultra‐performance liquid chromatography/tandem mass spectrometry (UPLC/MS/MS) method was developed in rat plasma and validated. The developed method requires a small volume of plasma (100 μL) and a simple liquid–liquid extraction. The chromatographic separations were achieved in 3.3 min using an Acquity UPLC BEH Shield RP 18 column. The mass spectrophotometric detection was carried out using a Waters Micromass Quattro MicroTM triple‐quadrupole system. Multiple reaction monitoring was used for the quantitation with transitions m / z 406 → m / z 181 for AZ66 and m / z 448 → m / z 285 for aripiprazole. The method was validated over a concentration range of 1–3500 ng/mL and the lower limit of quantitation was determined to be 1 ng/mL. Validation of the assay demonstrated that the developed UPLC/MS/MS method was sensitive, accurate and selective for the determination of AZ66 in rat plasma. The present method has been successfully applied to an i.v. pharmacokinetic study in Sprague–Dawley rats. Copyright © 2013 John Wiley & Sons, Ltd.