干旱区生态环境知识资源中心

A rapid and sensitive liquid chromatography-electrospray ionization tandem mass spectrometry method (LC-ESI-MS/MS) was developed and validated for the determination of goserelin in rabbit plasma. Various parameters affecting plasma sample preparation, LC separation, and MS/MS detection were investigated, and optimized conditions were identified. Acidified plasma samples were applied to Oasis (R) HLB solid-phase extraction (SPE) cartridges. Extracted samples were evaporated under a stream of nitrogen and then reconstituted with 100 mu L mobile phase A. The separation was achieved on a Capcell-Pak C18 (2.0 mm x 150 mm, 5 mu m, AQ type) column with a gradient elution of solvent A(0.05% acetic acid in deionized water/acetonitrile = 85/15; v/v) and solvent B (acetonitrile) at a flow rate of 250 mu L/min. The LC-MS/MS system was equipped with an electrospray ion source operating in positive ion mode. Multiple-reaction monitoring (MRM) of the precursor-product ion transitions consisted of m/z 635.7 -> m/z 607.5 for goserelin and m/z 424.0 -> m/z 292.1 for cephapirin (internal standard). The proposed method was validated by assessing specificity, linearity, limit of quantification (LOQ), intra-and inter-day precision and accuracy, recovery, and stability. Linear calibration curves were obtained in the concentration range of 0.1-20 ng/mL (the correlation coefficients were above 0.99). The LOQ of the method was 0.1 ng/mL Results obtained from the validation study of goserelin showed good accuracy and precision at concentrations of 0.1, 1, 5, 10, and 20 ng/mL. The validated method was successfully applied to a pharmacokinetic study of goserelin after a single subcutaneous injection of 3.6 mg of goserelin in healthy white rabbits. (C) 2010 Elsevier B.V. All rights reserved.