Determination of BMS-186318 in dog, rat and monkey plasma by liquid chromatography-ionspray mass spectrometry.
BMS-186318 is a member of the recently discovered "aminodiol" class of HIV protease inhibitors. A simple but sensitive method was developed for the determination of BMS-186318 in dog plasma and then applied to monkey and rat plasma. The compound was extracted from dog plasma with methyl tert-butyl ether at basic pH. The dried extract was reconstituted in mobile phase and injected into a 150 x 2.1 mm i.d. Zorbax Rx-C18 HPLC column. A portion of the effluent was directed into the LC-ionspray MS system, where the [M+H]+ ion of the secondary amine compound was monitored. The HPLC conditions were chosen in order to achieve a short run time and large sample throughput, with both analyte and internal standard eluting within 1.5 min. The liquid-liquid extraction procedure provided very clean extracts so that sufficient signal-to-noise ratio was obtained with single-stage mass spectrometry instead of the more costly tandem mass spectrometry. The required lower limit of quantitation of 2.5 ng ml-1 was easily achieved. The method has also been validated for BMS-186318 in monkey plasma without modification. The method has been modified for rat plasma. Owing to irreproducibility observed when applying the liquid-liquid extraction method to rat plasma, a solid-phase extraction method was developed. The addition of phenylmethylsulfonyl fluoride was necessary to stabilize BMS-186318 in rat blood and plasma.
Jemal
M
M
Department of Metabolism and Pharmacokinetics, Bristol-Myers Squibb Pharmaceutical Research Institute, Princeton, NJ 08543-4500, USA.
Hawthorne
D
D
D000818:Animals; D002138:Calibration; D002219:Carbamates / Q000097:blood*; D002851:Chromatography, High Pressure Liquid; D004285:Dogs; D004983:Ethanolamines / Q000097:blood*; D017320:HIV Protease Inhibitors / Q000097:blood*; D000882:Haplorhini; D007202:Indicators and Reagents; D013058:Mass Spectrometry; D011786:Quality Control; D051381:Rats; D013045:Species Specificity
C092415:BMS 186318; D002219:Carbamates; D004983:Ethanolamines; D017320:HIV Protease Inhibitors; D007202:Indicators and Reagents