HPLC法测定喷昔洛韦在健康人血浆浓度及其药代动力学研究

Determination of penciclovir concentration in plasma and study on its pharmacokinetics in Chinese healthy volunteers by HPLC

目的建立高效液相色谱法测定健康人血浆中喷昔洛韦（抗病毒药）浓度的方法，并研究其在健康人体的药代动力学。方法色谱柱为Agilent Zorbax SB-C18（4．6mm×150mm，5μm）。流动相为甲酸溶液和乙腈，用梯度洗脱方式，流量为1．0mL·min^-1。用该法研究10名健康受试者静脉滴注喷昔洛韦250mg的药代动力学。结果线性范围：血浆样品为0．05～5．00μg·mL^-1（7=0．9999）；尿样为0．1～20．0μg·mL^-1（7=0．9998）。血样及尿样的日内、日间皆RSD〈3％。其体内过程符合二室模型，其药代动力学参数：Cmax为（3．63±0．72）μg·mL^-1，AUC0-t为（7．67±1．10）μg·h·mL^-1。为（1．79±0．26）h，24h尿药累积排泄率为（73．9±15．6）％。结论此方法准确、简便、灵敏度高、专属性强，适用于临床药代动力学研究。

Objective To establish a HPLC methods for determination of peneielovir in human plasma and applied to study the pharmaeokineties in healthy volunteers. Methods The chromatographic separation was achieved on a Agilent Zorbax SB -CIS （4.6 mm × 150 mm, 5μ m）. The mobile phase consisted of formic acid solution and aeetonitrile at a flow rate of 1.0 mL · min^-1, a gradient separation was programmed. The pharmaeokinetie analysis of peneielovir in 10 volunteers after intravenous infusion of 250 mg peneielovir injection formulation was studied. Results A good linearity was obtained from O. 05 to 5. 00 μg · mL^- 1 in plasma （γ=0.9999）, and O. 1 to 20.0 μg · mL^-1 in urine （γ =0.9998）. The intraday and interday RSD were less than 3%. It was found to be fitted to a two - compartment open model and its pharmaeokinetie parameters were as follows ： Cmax was （ 3.63 ±0. 72 ） μg · mL^- 1, AUC0-t was （7.67 ± 1 .10） μg · h · mL^- 1 , t1/2β was （ 1.79 ± 0.26） h. The accumulate elimination rates of peneielovir in urine was （73. 9 ± 15.6 ） % after 24 h, respectively. Conclusion The method is accurate, convenient, sensitive, specific, and was suitable for the study of clinical pharmaeokineties, and the parameters in human provided a useful index for clinical practices.