Microsample determination of lovastatin and its hydroxy acid metabolite in mouse and rat plasma by liquid chromatography/ionspray tandem mass spectrometry.
A sensitive and specific method was developed and validated to quantitate lovastatin and its hydroxy acid in mouse and rat plasma. This method employs a solid-phase extraction procedure to isolate lovastatin and its hydroxy acid metabolite from the biological matrices (0.1 ml of mouse or rat plasma). The reconstituted extracts were analyzed by liquid chromatography/ionspray tandem mass spectrometry (LC/MS/MS). Simvastatin and simvastatin hydroxy acid were used as internal standards for lovastatin and lovastatin hydroxy acid, respectively. The assay has a lower limit of quantitation (LLQ) of 0.50 ng ml-1 in mouse and rat plasma for both lovastatin and its hydroxy acid based on 0.1 ml aliquots of plasma. The intra- and inter-assay precision (RSD), calculated from quality control (QC) samples, was < 7% for lovastatin and < 6% for lovastatin hydroxy acid in both matrices. The inter-assay accuracy as determined from QC samples was less than 6% for lovastatin and less than 8% for lovastatin hydroxy acid in both matrices. The overall recovery of lovastatin was 54% in mouse plasma and 55% in rat plasma, and the overall recovery of lovastatin hydroxy acid was 100% in mouse plasma and 67% in rat plasma.
Wu
Y
Y
Advanced BioAnalytical Services, Inc., Ithaca, New York 14850, USA.
Zhao
J
J
Henion
J
J
Korfmacher
W A
WA
Lapiguera
A P
AP
Lin
C C
CC
D000818:Animals; D002138:Calibration; D002853:Chromatography, Liquid; D003625:Data Collection; D006900:Hydroxylation; D000960:Hypolipidemic Agents / Q000097:blood*; D008148:Lovastatin / Q000031:analogs & derivatives / Q000097:blood*; D013058:Mass Spectrometry; D051379:Mice; D051381:Rats; D019821:Simvastatin
D000960:Hypolipidemic Agents; D008148:Lovastatin; D019821:Simvastatin