Majumdar, Tapan, Wu, Shari, Vedananda, Sunanda and Tse, Francis (2004) Determination of LAG078, a lipid-lowering compound, in dog plasma using liquid chromatography-tandem mass spectrometry: application in a toxicokinetic study. Journal of Pharmaceutical and Biomedical Analysis, 35 (4). pp. 853-866. ISSN 0731-7085

Abstract

A high throughput method was developed and validated for the quantitative determination of LAG078, a lipid-lowering compound, in dog plasma obtained during toxicokinetic studies. The method was based on reverse phase liquid chromatographic separation of the analyte from plasma extract followed by turbo-ionspray (TIS) in the negative ion mode and tandem mass spectrometry in the multiple reaction monitoring (MRM) mode. Extraction was performed using a combination of protein precipitation and liquid-liquid extraction in the 96-well plate format to increase the throughput of the method. Optimized chromatographic separation under basic condition (pH approximately 10) in a short polymer based column (50 mm x 2.0 mm i.d.) coupled with MRM mode of detection yielded clean chromatograms with minimal signal suppression. The standard curve was linear (r = 0.997) within the concentration range of 0.05 (lower limit of quantification; LLOQ) to 50 ng/ml using only 0.1 ml of dog plasma. The accuracy of the method varied from 95 to 100% with a precision (CV) of 3.04-10.8% over the concentration range. The method was simple, rapid, and robust.

Item Type:	Article
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Additional Information:	can archive post-print (ie final draft post-refereeing); Publisher's version/PDF cannot be used
Keywords:	LAG078; Lipid modulator; LDL; Lp(a); Turbo-ionspray; Tandem mass spectrometry
Related URLs:	http://www.ncbi.nlm.nih.gov/sites/entrez...
Date Deposited:	14 Dec 2009 14:07
Last Modified:	31 Jan 2013 01:31
URI:	https://oak.novartis.com/id/eprint/53