LC-MS/MS法测定Beagle犬血浆中曲札茋苷及其药动学研究  

Determination of piceatannol 3’-O-glucoside in the plasma of Beagle dogs using LC-MS/MS and its pharmacokinetic research

作　　者：汪庆 刘军锋 顾留歌 陈云建 秦燕[1] WANG Qing;LIU Jun-feng;GU Liu-ge;CHEN Yun-jian;QIN Yan(Shanghai Institute of Pharmaceutical Industry,China National Institute of Pharmaceutical Industry,State Key Laboratory of Innovative Medicines and Pharmaceutical Industry,Shanghai Professional Technical Serice Platform for Evaluation of Biomaterials'Pharmaceutical Propertes,Shanghai 200437,China;Kunyao Group Co.,Ltd.,Kunming 650100,China)

机构地区：[1]中国医药工业研究总院上海医药工业研究院创新药物与制药工艺国家重点试验室上海市生物物质成药性评价专业技术服务平台,上海200437 [2]昆药集团股份有限公司,昆明650100

出　　处：《中国新药杂志》2022年第1期82-88,共7页Chinese Journal of New Drugs

摘　　要：目的:建立LC-MS/MS法测定Beagle犬血浆中曲札茋苷的浓度,并用该方法研究其在Beagle犬体内的药动学特征。方法:以虎杖苷为内标,血浆样品采用甲醇沉淀的方式分离蛋白并离心取上清进样,色谱柱为Kromasil^(■)C_(18)柱(150 mm×2.1 mm)。以10 mmol·L^(-1)甲酸铵水溶液和乙腈为流动相,梯度洗脱,流速为0.3 mL·min^(-1)。监测的离子对分别为m/z 405.1~243.0(曲札茋苷)和m/z 389.1~226.9(虎杖苷)。Beagle犬采用静脉输注(iv gtt)的方式给予不同剂量的药物,不同时间点取样,测定其血浆中曲札茋苷的浓度。由DAS 2.0计算药动学参数。结果:血浆中曲札茋苷在1.0~200.0 ng·mL^(-1)范围内线性关系良好(r=0.9998),批内和批间精密度(RSD)均<15%。Beagle犬iv gtt给予不同剂量的曲札茋苷后,曲札茋苷的t_(1/2)为(53.3±15.5),(52.1±14.4)和(55.1±16.1)min,AUC_(0→t)为(15358±1815),(52401±3315)和(203419±43778)μg·min·L^(-1)。结论:本方法快速简便、灵敏度高、准确性好,适用于曲札茋苷的血药浓度测定和药动学研究。Objective: An LC-MS/MS method was established to determine the concentration of piceatannol 3’-O-glucoside in the plasma of Beagle dogs, which was further used for the pharmacokinetic characteristics. Methods: Polydatin was used as the internal standard. The plasma samples were precipitated by methanol. After centrifugation, the supernatant was injected for analysis. A Kromasil^(■) C_(18) column(150 mm×2.1 mm) was used with 10 mmol·L^(-1) ammonium formate aqueous solution and acetonitrile as mobile phases following a programmed gradient elution.The flow rate was set at 0.3 mL·min^(-1). The monitored ion pairs were m/z 405.1~243.0(piceatannol 3’-O-glucoside) and m/z 389.1~226.9(polydatin). Beagle dogs were administered different doses of drugs by intravenous infusion, and the plasma samples were taken at different time points to determine the concentration of piceatannol 3’-O-glucoside. The pharmacokinetic parameters were calculated by DAS 2.0. Results: Piceatannol 3’-O-glucoside in plasma had a good linear relationship in the range of 1.0~200.0 ng·mL^(-1)(r=0.999 8), and the intra-day and inter-day precision(RSD) were both within ±15%. After the Beagle dogs were given intravenous infusion of piceatannol 3’-O-glucoside at different doses, the t_(1/2) values of piceatannol 3’-O-glucoside were(53.3±15.5),(52.1±14.4) and(55.1±16.1) min, and AUC_(0→t) values were(15 358±1 815),(52 401±3 315) and(203 419±43 778) μg·min·L^(-1),respectively. Conclusion: This method is fast, simple, high in lucidity, and good in accuracy. It is suitable for the blood concentration determination and pharmacokinetic study of piceatannol 3’-O-glucoside.

关 键 词：曲札茋苷 BEAGLE犬血浆 LC-MS/MS 血药浓度 药动学研究 

分 类 号：R965[医药卫生—药理学]