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目的建立用于测定犬血浆中盐酸二甲双胍浓度的LC-MS/MS方法 ,比较3种盐酸二甲双胍制剂在Beagle犬体内药动学参数之间的差别。方法 6只Beagle犬,单剂量三周期分别口服3个剂型药物,按规定时间点取血样,血浆样品经乙腈沉淀蛋白,取上清液直接进行LC-MS/MS测定,以Zorbax SB-C_(18)(150 mm×2.1 mm,5μn)为色谱柱,V(乙腈):V(0.1%甲酸水溶液)=40:60为流动相,流速0.3 mL·min~(-1),柱温30℃,检测波长233 nm,并计算主要药动学参数。结果盐酸二甲双胍质量浓度在0.05～5 mg·L~(-1)内线性关系良好,回归方程为:y=0.686 8x-0.022 2(r=0.999 5),平均回收率为103.2%;盐酸二甲双胍普通片、盐酸二甲双胍缓释片和盐酸二甲双胍胃滞留片的主要药动学参数AUC_(0→t)分别为(97.01±5.36)、(134.6±10.2)、(204.0±19.2)mg·h·L~(-1),t_(max)分别为(2.612±1.35)、(5.869±0.95)、(7.105±1.33)h。结论将盐酸二甲双胍制成胃滞留缓释片可显著提高生物利用度;用LC-MS/MS法测定犬血中盐酸二甲双胍浓度,方法简单、快捷、灵敏、准确,适用于临床药动学及药效学的研究。
Objective To establish a LC-MS / MS method for the determination of metformin hydrochloride in canine plasma and to compare the pharmacokinetic parameters of three metformin hydrochloride preparations in Beagle dogs. Methods Six Beagle dogs were treated with three dosage forms orally three times a single dose for three weeks. The blood samples were taken from the plasma samples and the proteins were precipitated by acetonitrile. The supernatant was directly analyzed by LC-MS / MS. Zorbax SB-C_ (150 mm × 2.1 mm, 5μn) column with V (acetonitrile): V (0.1% formic acid in water) = 40:60 as mobile phase at a flow rate of 0.3 mL · min -1 , Detection wavelength 233 nm, and calculate the main pharmacokinetic parameters. Results The linear range of metformin hydrochloride was 0.05 ~ 5 mg · L -1. The regression equation was y = 0.686 8x-0.022 2 (r = 0.999 5) with the average recovery of 103.2%. Metformin hydrochloride was The main pharmacokinetic parameters of Metformin Hydrochloride Sustained-release Tablets and Metformin Hydrochloride Gastric Retention Tablets were (97.01 ± 5.36), (134.6 ± 10.2), (204.0 ± 19.2) mg · h · L-1, (-1) and t max were (2.612 ± 1.35), (5.869 ± 0.95) and (7.105 ± 1.33) h, respectively. Conclusions Metformin hydrochloride sustained-release tablets made of gastric retention can significantly improve the bioavailability; methotrexate hydrochloride concentration in canine blood by LC-MS / MS, the method is simple, fast, sensitive and accurate, suitable for clinical pharmacokinetics and drug Efficacy research.