Format

Send to

Choose Destination
Drug Test Anal. 2017 Aug;9(8):1236-1242. doi: 10.1002/dta.2156. Epub 2017 Apr 11.

Quantification of highly selective sigma-1 receptor antagonist CM304 using liquid chromatography tandem mass spectrometry and its application to a pre-clinical pharmacokinetic study.

Author information

1
Department of Pharmaceutics and Drug Delivery, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
2
Department of BioMolecular Sciences, School of Pharmacy, The University of Mississippi, University, MS, 38677, USA.
3
Department of Radiology, Stanford University, Stanford, CA, 94305, USA.

Abstract

An ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for quantification of CM304, a novel and highly selective sigma-1 receptor antagonist that has recently entered into human clinical trials. A structural analogue of CM304, SN56, was used as the internal standard (IS). Chromatographic separation was achieved on an Acquity UPLC™ BEH C18 (1.7 μm, 2.1 mm × 50 mm) column using a mobile phase [water:methanol (0.1%v/v formic acid; 50:50, %v/v)] at a flow rate of 0.2 mL/min. Mass spectrometric detection was performed in the positive ionization mode with multiple reaction monitoring (MRM) using m/z transitions of 337 > 238 for CM304 and 319 > 220 for the IS. The method was found to be linear and reproducible with a regression coefficient consistently >0.99 for the calibration range of 3 to 3000 ng/mL. The extraction recovery ranged from 91.5 to 98.4% from spiked (7.5, 300 and 2526 ng/mL) plasma quality control samples. The precision (%RSD; 1.1 to 2.9%) and accuracy (%RE; -1.9 to 1.8%) were within acceptable limit. The validated method was successfully applied to a single dose oral and intravenous (I.V.) pharmacokinetic study of CM304 in rats. Following I.V. administration, the compound exhibited adequate exposure along with high extravascular distribution and insignificant amount of extra hepatic metabolism.

KEYWORDS:

CM304; UPLC-MS/MS; bioanalysis; cocaine addiction

PMID:
28039926
DOI:
10.1002/dta.2156
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Wiley
Loading ...
Support Center