医药学论文：HPLC法测定阿莫西林舒巴坦酯片人体血药浓度

【摘要】 目的 建立阿莫西林舒巴坦酯片中阿莫西林和舒巴坦的血药浓度测定方法。方法 以色谱柱为Spberiserb ODS(Φ3.9mm×200mm,5μm)；流动相为乙腈-0.068mol/L KH2PO4(4.5：95.5)；流速为0.8ml/min;检测浓度为225nm;柱温为（25±0.1）℃方法测定人体内阿莫西林血药浓度。以色谱柱为Hypersil C18(Φ4.6mm×200mm，5μm)；流动相为乙腈-0.068mol/L KH2PO4(4.5：95.5);流速为1.2ml/min;检测波长为210nm;柱温为（25±0.1）℃方法测定人体内舒巴坦血药浓度。结果 阿莫西林和舒巴坦在选定的色谱分离条件下，与血浆中杂质峰分离良好，分离度大于1.5。阿莫西林血浆药物浓度在0.125～10μg/ml范围内线性良好，r=0.9998;舒巴坦血浆药物浓度在0.10～10μg/ml范围内线性良好，r=0.9999。阿莫西林和舒巴坦的平均回收率分别为96.25%、102.3%。两种成分的日内、日间RSD＜10%。结论 HPLC法测定方人体内阿莫西林和舒巴坦血药浓度方法准确度精度和灵敏度均较高，符合血浆中药物测定要求。

 

【关键词】 阿莫西林舒巴坦酯片；高效液相色谱法；血药浓度

 

To detect human blood concentration of amoxicillin and sulbactam with HPLC

 

【Abstract】 Objective To set up the detection method of human blood concentration of amoxicillin and sulbactam. Methods The chromatographic column was Spberiserb ODS(φ3.9mm×200mm.5μm ),and the mobile phase was acetonitrile- 0.068mol/L KH2PO4(4.5:95.5),the flow rate was 0.8ml/min,the detection wavelength was 225nm,and the column temperature was 25±0.1 ℃.We detected the human blood concentration of amoxicillin,the chromatographic colum was Hypersil C18(φ4.6mm×200mm 5μm),the mobile phase was acetonitrile-0.068mol/L KH2po4(4.5:95.5),the flow rate was 1.2ml/min,the detection wavelength was 210nm, and the column temperature was 25±0.1 ℃.We detected the human blood concentration of sulbactam. Results We found that amoxicillin and sulbactam were under the condition of selected chromatographic separation, the resolution of amoxicillin and sulblactam and the impurity in the blood plasma was favorable.The resolution was < 1.5,the human blood concentration of amoxicillin was 0.125～10μg/ml, and the linear regrossion was favorable,r=0.9998.The human blood concentration of sulbactam was 0.10～10μg/ml,and the linear regrossion was favorable,r=0.9999.The average recovery of amoxicillin and sulbactam were 96.25%and 102.3%.The two kinds of components were RSD< 10%in a day or next.Conclusion The study shows that we can detect the human blood concentration of amoxicillin and sulbactam with HPLC,and the method has very good accuracy,precision and sensitivity.It is accord with demands of drug detection.

 

【Key words】 amoxicillin and sulbactam;liquid chromatography;blood concentration

 

阿莫西林舒巴坦酯是由阿莫西林和舒巴坦以共价键结合形成的化合物，阿莫西林为广谱的β-内酰胺类青霉素，舒巴坦是β-内酰胺酶抑制剂，无抑菌活性，能够抑制细菌产生的Ⅱ型～Ⅳ型β-内酰胺酶，使阿莫西林免受酶的水解灭活，从而增加阿莫 西林对细菌的敏感性。该药口服后在胃肠上壁被非 特异酯酶分解为阿莫西林和舒巴坦，并吸收进入人体血液循环［1］。临床上主要用于治疗上、下呼吸道感染和皮肤、软组织感染及性病等［2］。本文研究阿莫西林舒巴坦片口服后血浆中阿莫西林和舒巴坦药物浓度测定方法，为该制剂的人体药代动力学和生物学等效性研究及临床用药提供参考。

 

1 材料与方法

 

1.1 药品与试剂 阿莫西林对照品（中国药品生物制品检定所，含量86.2%、批号0409-9706）；舒巴坦对照品（中国药品生物制品检定所，含量99.8%、批号0430-9501）；阿莫西林舒巴坦酯片（珠海联邦制药有限公司中山分厂生产，每片含阿莫西林250mg、舒巴坦250mg，批号030418）；乙腈为色谱纯；乙醚、磷酸二氢钾、盐酸高氯酸为分析纯；水为超纯水。