Determination of lovastatin hydroxy acid in female B6C3F1 mouse serum.
A liquid chromatographic-mass spectrometricmethod for the determination of lovastatin hydroxy acid in female B6C3F(1) mouse serum was developed for use in supporting toxicokinetic studies of animals dosed with the cholesterol lowering agent lovastatin. The method does not require an extensive sample cleanup and shows good correlation between serum matrix standards and solvent standards. The method was validated and used to analyze serum samples from a preliminary dose level range-finding study. The method was validated for a concentration range of approximatel 1.0 to 100 ng/mL in serum, and linearity was verified to ~2000 ng/mL. The stability of sample extracts was determined under various storage conditions and the stability of serum samples stored frozen was determined over a period of seven weeks. During the course of analyzing the animal samples, the serum was monitored for the presence of lovastatin not hydrolyzed to the hydroxy acid, but no attempt was made to quantify lovastatin. No unhydrolyzed lovastatin was noted in any of the serum samples from animals dosed with lovastatin.
Lodge
Jon W
JW
RTI International, P.O. Box 12194, Research Triangle Park, North Carolina 27709-2194, USA.
Fletcher
Brenda L
BL
Brown
Sherri S
SS
Parham
Angela J
AJ
Fernando
Reshan A
RA
Collins
Bradley J
BJ
D000818:Animals; D000924:Anticholesteremic Agents / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid; D005260:Female; D006880:Hydroxy Acids / Q000097:blood*; D008148:Lovastatin / Q000493:pharmacokinetics*; D051379:Mice; D008815:Mice, Inbred Strains; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000924:Anticholesteremic Agents; D006880:Hydroxy Acids; D008148:Lovastatin