大鼠尿液中阿仑膦酸钠的柱前衍生化HPLC-UV测定法及药动学应用

发布时间：2019-02-13 17:01

【摘要】：目的:建立大鼠尿液中阿仑膦酸钠柱前衍生HPLC-UV测定方法,并应用于大鼠口服阿仑膦酸钠后尿液排泄动力学研究。方法:大鼠单次灌胃给予阿仑膦酸钠溶液(4.5 mg·kg~(-1)),在给药后不同时间段收集尿液,尿液固相萃取预处理后,采用异硫氰酸苯酯(PITC)对尿液中的阿仑膦酸钠衍生化。液相色谱分析采用Venusil AA分析柱(4.6 mm×250 mm,5μm),以乙酸钠溶液-乙腈为流动相,梯度洗脱,正亮氨酸为内标,流速0.8 mL·min~(-1),检测波长270 nm。结果:阿仑膦酸钠质量浓度在2.5~250.0μg·mL~(-1)范围内线性良好(r=0.999);方法的日内和日间精密度小于3.0%,提取回收率在87.5%~89.2%之间;检测限为0.2μg·mL~(-1)。尿液排泄动力学曲线显示阿仑膦酸钠溶液口服后达峰时间约为2.16 h,清除半衰期为(4.5±0.12)h,36 h尿液累积量为(42.6±1.2)μg,占给药剂量的4.7%。结论:本方法经方法学验证,可用于阿仑膦酸钠尿液排泄动力学研究。
[Abstract]:Aim: to establish a HPLC-UV method for the determination of alendronate in rat urine by precolumn derivatization and to study the urinary excretion kinetics of alendronate in rats after oral administration of alendronate. Methods: rats were given alendronate sodium solution (4.5 mg kg~ (-1),) by single gavage). Urine was collected at different time points after administration, and the urine was pretreated with solid phase extraction (SPE). Sodium alendronate in urine was derivatized by isothiocyanate (PITC). Venusil AA column (4.6 mm 脳 250 mm,5 渭 m),) with sodium acetate solution-acetonitrile as mobile phase, gradient elution, n-leucine as internal standard, flow rate 0.8 mL min~ (-1), detection wavelength 270 nm. Results: the calibration curve of alendronate was linear in the range of 2.5 渭 g mL~ (-1) and 250.0 渭 g mL~ (-1), the precision of the method was less than 3.0 and the recovery rate was 87.5% or 89.2%. The detection limit was 0.2 渭 g mL~ (-1). The urine excretion kinetics curve showed that the peak time of alendronate solution was about 2.16 h after oral administration, and the clearance half-life was (4.5 卤0.12) h ~ (36) h urine accumulation was (42.6 卤1.2) 渭 g, accounting for 4.7% of the dosage given. Conclusion: this method can be used in the study of urinary excretion kinetics of alendronate.
【作者单位】：南昌大学药学院;
【基金】：江西省自然科学基金资助项目(20142BAB205026) 南昌大学研究生创新专项资金资助(cx2015155)
【分类号】：R965

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