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目的:采用LC-MS/MS测定静脉注射、灌胃粉防己碱原料药与皮下注射粉防己碱凝胶剂的血药浓度,计算粉防己碱凝胶剂的生物利用度。方法:建立血浆中粉防己碱含量的检测方法。通过颈静脉注射粉防己碱原料药、灌胃原料药、皮下注射凝胶剂后采血,采用LC-MS/MS检测大鼠血浆中药物浓度,流动相0.1%甲酸水溶液-乙腈梯度洗脱,流速0.4 m L·min-1;采用电喷雾电离,正离子检测模式,粉防己碱和蝙蝠葛碱(内标)的m/z分别为623.1~176.0,625.1~206.0。利用DAS 3.0软件计算药动学参数并绘制药-时曲线,计算口服和皮下注射方式的绝对生物利用度。结果:建立的LC-MS/MS精密度、稳定性良好(RSD均<11.0%),萃取回收率81.36%~97.14%。灌胃给予粉防己碱与皮下注射粉防己碱凝胶剂的绝对生物利用度分别为42.76%和85.44%。结论:粉防己碱凝胶剂的生物利用度较灌胃给予原料药大大提高,且具有缓释效果,具有一定的开发前景。
OBJECTIVE: To determine the bioavailability of tetrandrine gel by LC-MS / MS, and determine the plasma concentration of tetrandrine and subcutaneous injection of tetrandrine gel. Methods: To establish a method for the determination of tetrandrine in plasma. The drug was injected into the jugular vein, gavage of the drug substance and injection of the gelatin solution. LC-MS / MS was used to determine the concentration of the drug in the plasma of the rat. The mobile phase consisted of a 0.1% formic acid-acetonitrile gradient and the flow rate 0.4 m L · min-1. The m / z of tetrandrine and dauricine (internal standard) were 623.1 ~ 176.0 and 625.1 ~ 206.0 respectively by electrospray ionization and positive ion detection. Pharmacokinetic parameters were calculated using the DAS 3.0 software and drug-time curves were plotted to calculate the absolute bioavailability of oral and subcutaneous injections. Results: The established LC-MS / MS had good precision and good stability (RSD <11.0%), and the extraction recovery was 81.36% -97.14%. The absolute bioavailability of tetrandrine and subcutaneously injected tetrandrine gels were 42.76% and 85.44%, respectively. CONCLUSION: The bioavailability of tetrandrine gel is significantly higher than that given by gavage. It has slow release effect and certain development prospects.