title: Determination of LAG078, a lipid-lowering compound, in dog plasma using liquid chromatography-tandem mass spectrometry: application in a toxicokinetic study.
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.
authors.affiliation: Department of Preclinical Safety, Novartis Institute for Biomedical Research, Building 405, Room 228, One Health Plaza, Novartis, East Hanover, NJ 07936, USA. tapan.majumdar@pharma.novartis.com
authors.forename: Tapan K
authors.initials: TK
authors.lastname: Majumdar
authors.forename: Shari
authors.initials: S
authors.lastname: Wu
authors.forename: Sunanda
authors.initials: S
authors.lastname: Vedananda
authors.forename: Francis L S
authors.initials: FL
authors.lastname: Tse
mesh_terms: D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods; D004285:Dogs; D006845:Hydrocarbons, Fluorinated / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity; D000960:Hypolipidemic Agents / Q000097:blood* / Q000493:pharmacokinetics* / Q000633:toxicity; D013058:Mass Spectrometry / Q000379:methods; D013457:Sulfur Compounds / Q000097:blood* / Q000493:pharmacokinetics / Q000633:toxicity
chemical_list: D006845:Hydrocarbons, Fluorinated; D000960:Hypolipidemic Agents; C495407:LAG078; D013457:Sulfur Compounds