Pharmazeutische Analytische Chemie: Offener Zugang
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LC-ESI-MS/MS-Bestimmung von GSK-199, einem neuen reversiblen PAD4-Inhibitor in Mäuseplasma und seine Anwendung in einer pharmakokinetischen Studie an Mäusen

Gurulingappa Hallur, Buchi Reddy Purra, Jeyaraj Duraiswamy A, Suresh Sulochana P, Pavan Kumar Nagasuri VSP, Rudresh Gangaiah, Mohd Zainuddin, Sriram Rajagopal und Ramesh Mullangi

A simple, specific, sensitive and rapid LC-ESI-MS/MS method has been developed and validated for the quantification of GSK-199 in mice plasma using warfarin as an internal standard (IS). Sample preparation was accomplished through a liquid-liquid extraction process. Chromatographic separation of GSK-199 and IS was performed on a Chromolith column using an isocratic mobile phase comprising 0.2% formic acid in water and acetonitrile (25:75, v/v) at a flow rate of 1.0 ml/min. Elution of GSK-199 and IS occurred at ~1.32 and 1.81 min, respectively. The total chromatographic run time was 2.50 min. A linear response function was established in the concentration range of 2.52-1009 ng/ml. Method validation was performed as per regulatory guidelines and the results met the acceptance criteria. The intra- and inter-day accuracy and precision were in the range of 1.75-12.3 and 4.99-12.3%, respectively. GSK-199 was found to be stable under various stability conditions. This novel method has been applied to a pharmacokinetic study in mice.