HPLC-荧光法测定α-细辛醚热熔压敏胶贴剂的相对生物利用度

目的: 建立家兔血浆内α-细辛醚的HPLC-荧光测定法,研究α-细辛醚热熔压敏胶贴剂在家兔体内的相对生物利用度。 方法: 家兔给予α-细辛醚混悬液或α-细辛醚贴剂后于不同时间点采血,血浆样品处理后以甲醇-水(75∶ 25)为流动相,使用ZORBAX Eclipse XDB-C₁₈色谱柱(250 mm×4.6 mm,5 μm)进行分离,流速1.0 mL·min^-1,荧光检测器激发波长为265 nm,检测波长为365 nm,测定血浆药物浓度,计算药物动力学参数和相对生物利用度。 结果: α-细辛醚在浓度0.01~1 μg·mL^-1(r=0.9998)范围内线性关系良好,检测限为0.005 μg·mL^-1,方法学回收率为96.2%~102.0%,日内与日间RSD均＜4.5%。家兔口服α-细辛醚混悬液后的AUC_0→t为(0.53±0.23)μg·h·mL^-1,贴剂给药的AUC_0→t为(7.86±2.15)μg·h·mL^-1,贴剂的相对生物利用度为1494%。 结论: 该法简便准确,可用于家兔血浆内α-细辛醚浓度的测定;α-细辛醚热熔压敏胶贴剂的相对生物利用度高。

Objective: To establish an HPLC method for the determination of α-asarone in rabbit plasma and to study the relative bioavailability of hot melt pressure sensitive adhesive patch. Methods: The plasma samples were collected at the predetermined time points after oral or transdermal administration.The plasma concentrations of α-asarone were determined by HPLC method using ZORBAX Eclipse XDB-C₁₈(250 mm×4.6 mm,5 μm) column,methanol-water (75∶ 25) as mobile phase,flow rate at 1.0 mL·min^-1 after pretreatment.The excitation wavelength and emission wavelength were 265 nm and 365 nm,respectively.The pharmacokinetics and relative bioavailability were studied. Results: A good linearity was obtained in the range of 0.01-1 μg·mL^-1 (r=0.9998) with a detective limit of 0.005 μg·mL^-1.The method recovery was between 96.2%-102.0%.The relative standard deviations of within-day and between-day were less than 4.52%.The AUC_0→t of α-asarone after oral and transdermal administration were (0.53±0.23)μg·h·mL^-1and (7.86±2.15)μg·h·mL^-1,respectively;the relative bioavailability of patch was 1494%. Conclusion: The established method is simple,accurate and suitable for the determination of α-asarone in rabbit plasma.The hot melt pressure sensitive adhesive patch containing α-asarone had shown high relative bioavailability.