A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard）...A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard） were extracted from nude mice plasma samples by liquid-liquid extraction. Separation was achieved on a reversed phase ClS column with a mobile phase of acetonitrile-water （35：65, v/v） containing 5 mM ammonium formate （pH = 3.0）. All compounds were monitored by mass spectrometry with electrospray positive ionization. The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error, which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67% for OSI-420; precision was validated by relative standard deviation, which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420. This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg. A 2-compartment model was used to fit the pharmacokinetics of erlotinib and 1-compartment model for the pharmacokinetics of OSI-420. The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.展开更多
基金National Integrity Innovational Technology Platform of New Drug and Development (Grant No. 2009ZX09301-010)Innovation Team of Ministry of Education (Grant No. BMU20110263)
文摘A simple, rapid and sensitive LC-MS/MS method was developed to quantify erlotinib and its active metabolite, OSI-420, simultaneously in BALB/c nude mice plasma. Erlotinib, OSI-420 and propranolol （internal standard） were extracted from nude mice plasma samples by liquid-liquid extraction. Separation was achieved on a reversed phase ClS column with a mobile phase of acetonitrile-water （35：65, v/v） containing 5 mM ammonium formate （pH = 3.0）. All compounds were monitored by mass spectrometry with electrospray positive ionization. The lower limit of quantification was 0.5 ng/mL for both erlotinib and OSI-420; accuracy was estimated by relative error, which was in the range from 0.07% to 8.00% for erlotinib and -2.83% to 6.67% for OSI-420; precision was validated by relative standard deviation, which was from 2.28% to 15.12% for erlotinib and from 1.96% to 11.50% for OSI-420. This method was applied to a pharmacokinetic study of BALB/c nude mice following oral administration of erlotinib at 12.5 mg/kg. A 2-compartment model was used to fit the pharmacokinetics of erlotinib and 1-compartment model for the pharmacokinetics of OSI-420. The ratio of the active metabolite to parent drug in mice was greater than previously reported in humans and probably reflects interspecies difference in the rate of conversion of erlotinib to OSI-420.
