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目的建立离子交换色谱法人血浆和尿液中盐酸二甲双胍浓度的测定方法,并应用于人体药代动力学研究。方法血浆样本采用加入含有内标(马来酸氯苯那敏)的乙腈溶液沉淀蛋白,离心后的上清液置40℃水浴下氮气挥干,残渣用流动相复溶,涡旋混合,高速离心后吸取上清液进样分析。色谱柱:Capcell PAK SCX UG80(4.6 mm×150 mm,5μm);流动相:乙腈-0.15 mol·L~(-1)磷酸二氢铵(用10%磷酸调至:p H 3)=52∶48;流速:1 m L·min~(-1);柱温:35℃;检测波长:233 nm。尿液样本用超纯水稀释后直接进HPLC分析。结果二甲双胍的血浆和尿液样本的线性范围分别为0.05~5μg·mL~(-1)(r=0.999 3)和0.20~200μg·mL~(-1)(r=0.999 1);最低定量下限分别为0.05,0.20μg·mL~(-1);回收率分别为88.65%~95.42%和91.22%~108.18%;日内和日间RSD均<15%;血浆和尿液质控样本在稳定性考察范围内均良好。结论该方法适用性广、准确性好、专属性强、重现性好且快速灵敏,适用于盐酸二甲双胍片的药代动力学研究。
OBJECTIVE To establish a method for the determination of metformin hydrochloride in human plasma and urine by ion exchange chromatography and to study its pharmacokinetics. Methods The plasma samples were precipitated by adding acetonitrile with internal standard (chlorpheniramine maleate). After centrifugation, the supernatant was evaporated to dryness in a water bath at 40 ° C. The residue was reconstituted with a mobile phase, vortexed, After centrifugation, the supernatant was taken for injection analysis. Column: Capcell PAK SCX UG80 (4.6 mm × 150 mm, 5 μm); mobile phase: acetonitrile-0.15 mol·L -1 ammonium dihydrogen phosphate (adjusted to pH 3 with 10% phosphoric acid) 48; flow rate: 1 m L · min -1; column temperature: 35 ℃; detection wavelength: 233 nm. Urine samples diluted with ultrapure water directly into the HPLC analysis. Results The linear range of plasma and urine samples of metformin was 0.05 ~ 5μg · mL -1 (r = 0.999 3) and 0.20 ~ 200μg · mL -1 (r = 0.999 1) respectively. The lowest limit of quantitation Respectively, the recoveries were 88.65% -95.42% and 91.22% -108.18%, respectively. The intra-day and inter-day RSD were all less than 15%. The plasma and urine samples were stable in stability The scope of investigation are good. Conclusion The method has wide applicability, good accuracy, strong specificity, good reproducibility and sensitivity. It is suitable for the pharmacokinetic study of metformin hydrochloride tablets.