LC-MS法快速测定尼群地平纳米结晶制剂在Beagle犬中的血药质量浓度

Rapid determination of nitrendipine concentration in Beagle dogs plasma using LC-MS

目的建立一种液相色谱质谱联用(LC-MS)方法,用于快速测定Beagle犬血浆中尼群地平的质量浓度。方法血浆样品采用液-液萃取法提取,色谱柱为Kinetex XB-C18柱(50 mm×2.1 mm,2.6μm),流动相为乙腈-体积分数0.2%甲酸溶液(体积比为70∶30)。质谱在ESI正离子模式下以多反应监测扫描方式检测。结果尼群地平的线性范围为1~500μg·L^(-1),日内和日间RSD均小于10%,准确度(RE)为-5.7%~0.1%,提取回收率大于90%,基质效应在86.11%~103.4%内。尼群地平在Beagle犬血浆中的主要药动学参数:tmax为(2.5±0.5)h;ρmax为(139.0±4.6)μg·L^(-1);t1/2为(7.1±0.9)h;AUC(0-48)为(891.4±157.1)μg·L^(-1)·h,AUC(0-∞)为(906.9±152.1)μg·L^(-1)·h。结论该测定方法适用于尼群地平纳米结晶制剂在Beagle犬体内的药物动力学研究。

Objective To establish a liquid chromatography-tandem mass spectrometry （LC-MS）method for the rapid determination of nitrendipine in the plasma of Beagle dogs. Methods Nitrendipine was extracted using a liquid-liquid extraction method. The chromatographic separation was accomplished on a Kinetex XB- C18 column（50 mm ×2.1 mm,2. 6μm） using a mobile phase of acetonitfile -0. 2% formic acid（ V： V=70： 30）. Multiple reaction monitoring transitions were performed under ESI positive ionization. Results The linear calibration curves were obtained over the concentration range of 1 - 500μg·L^-1 with the intra-and inter-day precision both less than 10%. The accuracy ranged from-5.7% to 0. 1% in terms of relative error （RE）, and the extraction recoveries were more than 90%. The matrix effects were between 86. 11% and 103.4%. The main pharmacokinetics parameters of nitrendipine in the plasma of Beagle dogs were as followS：tmax （ 2. 5 ± 0. 5 ） h; Pmax （ 139.0 ± 4. 6 ） μg·L^-1 ; t1/2 （ 7.1 ± 0. 9 ） h, AUC（0-48） （ 891.4 ± 157. 1 ） μg·L^-1. h, AUC（0-∞ ） （906. 9 ± 152. 1 ）μg·L^-1. h, respectively. Conclusions The established LC-MS method is simple and sensitive, and it was successfully applied to the pharmacokinetics studies of nitrendipine nanocrystals in Beagle dogs.