LC-MS/MS法测定Beagle犬血浆中去甲文拉法辛的质量浓度

Determination of desvenlafaxine in Beagle dogs plasma by LC-MS/MS

目的建立液质联用法测定Beagle犬血浆中去甲文拉法辛的质量浓度,并应用该方法研究琥珀酸去甲文拉法辛缓释片在Beagle犬体内的药代动力学行为。方法采用液液萃取法处理血浆样品,色谱柱选择Venusil ASB C_(18)柱,以甲醇-浓度5 mmol·L^(-1)醋酸铵缓冲溶液(体积比35∶65)为流动相,采用多反应离子监测(multiple reaction monitoring,MRM)扫描方式进行检测。结果去甲文拉法辛的质量浓度在0.50~100μg·L^(-1)内与峰面积线性关系良好,相关系数r为0.999 0,日内和日间精密度RSD≤6.2%,去甲文拉法辛的提取回收率在79.6%~83.3%内,基质效应在96.5%~98.8%内。结论本方法适用于琥珀酸去甲文拉法辛缓释片在Beagle犬体内药代动力学行为的研究。

Objective To develop a rapid,sensitive and specific liquid chromatography-tandem mass spectrometry（ LC-MS /MS） method for the determination of desvenlafaxine in Beagle dogs plasma,and to study the pharmacokinetic characteristic of desvenlafaxine succinate in Beagle dogs plasma. Methods The chromatographic separation was accomplished on Agela C_（18） analytical column with the mobile phase consisting of methanol-5 mmol·L^-1 ammonium acetate（ V∶ V = 35∶ 65）. Liquid-liquid extraction was used for the sample pretreatment. The plasma concentration of desvenlafaxine was detected by multiple reaction monitoring（ MRM） after the Beagle dogs were given desvenlafaxine succinate extended-release tablets.Results The linear calibration curve of desvenlafaxine was obtained in the concentration range of0. 500^-100 g·L^-1. The correlation coefficient was 0. 999 0. The intra-and inter-assay precision were both less than 6. 2%. The average recoveries were between 79. 6% and 83. 3%. The matrix effects were between96. 5% and 98. 8%. Conclusions This rapid,sensitive and specificliquid chromatography-tandem mass spectrometry（ LC-MS /MS） method is successfully applied to pharmacokinetic studies of desvenlafaxine succinate in Beagle dogs plasma.