科研之友
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摘要
A sensitive and selective UPLC-MS/MS method for determination of letrozole in rat plasma was developed. After addition of midazolam as internal standard (IS), protein precipitation by acetonitrile-methanol (9: 1, v/v) was used as sample preparation. Chromatographic separation was achieved on a C18 column (2.1 mm x 100 mm, 1.7 mu m) with acetonitrile-0.1% formic acid in water as mobile phase with gradient elution. An electrospray ionization source was applied and operated in positive ion mode; multiple reaction monitoring (MRM) mode was used for quantification using target fragment ions m/z 286.2 -> 217.1 for letrozole and m/z 326.0 -> 291.0 for IS. Calibration plots were linear over the range of 22000 ng/mL for letrozole in rat plasma. Mean recoveries of letrozole in rat plasma were in the range of 77.9-79.5%. RSD of intra-day and inter-day precision were both < 12%. The method was successfully applied to pharmacokinetic study of letrozole after oral administration of single dosage 25 mg/kg in rats.
