液相色谱-串联质谱法测定比格犬血浆中氢吗啡酮

目的建立快速、灵敏的液相色谱-串联质谱法测定比格犬血浆中氢吗啡酮。方法比格犬血浆0.1 mL经β-葡糖苷酸酶孵化16 h后，采用液-液萃取法处理，以甲醇-水-甲酸(65∶35∶2〗1)为流动相，Zorbax SB C₈柱分离，采用大气压化学电离源，选择反应监测（SRM）。结果测定氢吗啡酮的线性范围为0.80-200.0 μg·L^-1，定量下限为0.80 μg·L^-1。日内、日间精密度（RSD）均小于6.0%，准确度（RE）在±1%以内。应用此法研究了6只比格犬单剂量po盐酸氢吗啡酮缓释片4 mg后的药代动力学特征。结论该法选择性强、灵敏度高，适用于氢吗啡酮缓释制剂的药代动力学研究。

Determination of hydromorphone in Beagle dogs plasma by liquid chromatography-tandem mass spectrometry

AIM: To establish a LC/MS/MS method for determination of hydromorphone (HYD) in Beagle dog plasma. METHODS: After incubation with beta-glucuronidase for 16 h, an aliquot of 0.1 mL plasma was treated by liquid-liquid extraction. The analytes of interest were separated on a Zorbax SB C8 column with the mobile phase consisting of methanol-water- formic acid (65: 35: 1). Atmospheric pressure chemical ionization source of MS was applied and operated in positive ion mode. RESULTS: The linear calibration curve was obtained in the concentration range of 0.80 - 200.0 microg x L(-1). The lower limit of quantification was 0.80 microg x L(-1). The inter-day and intra-day precision (RSD) was below 6.0%, and the accuracy (RE) was within 1% calculated from QC samples. The method was used to determine the pharmacokinetic parameters of HYD after a single oral administration of 4 mg HYD sustained release tablets to Beagle dogs. CONCLUSION: The method was proved to be specific, sensitive, and suitable for the pharmacokinetic study of HYD sustained release formulation.