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目的:建立简便、灵敏的检测人血浆中青藤碱浓度的高效液相色谱-三重四极杆质谱联用技术(HPLC-MS/MS),研究健康受试者口服芪麝丸后青藤碱的体内药代动力学特征。方法:血浆样品中加入内标(普萘洛尔),加甲醇沉淀蛋白后分离上清液进行检测,流动相甲醇-水(含0.1%甲酸+5 mmol·L~(-1)甲酸铵)进行梯度洗脱。质谱采用电喷雾电离源(ESI),选择反应离子监测模式,用于定量分析的青藤碱和普萘洛尔离子对的m/z分别为(330.2~152.2和260.2~183.1)。利用Win Nonlin 6.3软件计算人口服芪麝丸后青藤碱的药动学参数。结果:人血浆中青藤碱线性范围5~1 000μg·L~(-1),定量下限5.0μg·L~(-1),批内和批间准确度偏差均在±10.0%以内,RSD均<15.0%,青藤碱的回收率103.3%,无明显基质效应,稳定性良好。人口服芪麝丸后血浆中青藤碱的主要药动学参数达峰时间(T_(max)),药峰浓度(C_(max)),药时曲线下面积(AUC_(0-48 h)),半衰期(t_(1/2))分别为(2.5±0.8)h,(477.9±60.1)μg·L~(-1),(4 808.8±791.7)h·μg·L-1,(7.5±1.3)h。结论:建立的方法简便、快速、灵敏、可靠,可用于研究人口服芪麝丸后青藤碱的药代动力学特征,为该制剂的致敏机制和药代-药效研究提供一定的方法学基础和数据。
Objective: To establish a simple and sensitive method for the determination of sinomenine in human plasma by high performance liquid chromatography-triple quadrupole mass spectrometry (HPLC-MS / MS) and to study the effect of sinomenine In vivo pharmacokinetic characteristics. Methods: The internal standard (propranolol) was added to the plasma samples, and the supernatant was separated by precipitation with methanol. The mobile phase was methanol - water (containing 0.1% formic acid and 5 mmol·L -1 ammonium formate) Gradient elution. The electrospray ionization source (ESI) was used for the mass spectrometry, and the mode of reaction monitoring was selected. The m / z of sinomenine and propranolol ion pair for quantitative analysis were (330.2-152.2 and 260.2-183.1), respectively. Win Nonlin 6.3 software was used to calculate the pharmacokinetic parameters of sinomenine after human oral administration of qi musk pills. Results: The linear range of sinomenine in human plasma ranged from 5 to 1 000 μg · L -1 and the limit of quantification was 5.0 μg · L -1. The accuracy of intra-and inter-batch deviations was within ± 10.0%. RSD All <15.0%, sinomenine recovery 103.3%, no obvious matrix effect, good stability. The main pharmacokinetic parameters of plasma sinomenine peak time (T_ (max)), drug peak concentration (C_ (max)) and the area under the curve of time after drug administration (AUC 0-48 h) (2.5 ± 0.8) h, (477.9 ± 60.1) μg · L -1, (4 808.8 ± 791.7) h · μg · L -1, respectively) and half life (t 1/2) ± 1.3) h. CONCLUSION: The established method is simple, rapid, sensitive and reliable and can be used to study the pharmacokinetics of sinomenine after oral administration of Qijishan Pill. It provides a method for the study of sensitization mechanism and pharmacokinetics-pharmacodynamics of this preparation Learn the basics and data.