Determination of LAG078, a lipid-lowering compound, in dog plasma using liquid chromatography-tandem mass spectrometry: application in a toxicokinetic study.
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 |
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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 |
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Date Deposited: | 14 Dec 2009 14:07 |
Last Modified: | 31 Jan 2013 01:31 |
URI: | https://oak.novartis.com/id/eprint/53 |