HPLC测定人血浆中螺旋霉素的浓度及其药代动力学研究

Determination of spiramycin in human plasma by HPLC and the pharmacokinetic study

目的 :建立人血浆中螺旋霉素 (SPM )浓度的测定方法及进行人体药代动力学的研究。方法 :采用高效液相色谱法 ,色谱柱 :phenomenex C1 8色谱柱 (5 μm,2 5 0 mm× 4 .6 mm) ,以乙腈∶磷酸二氢钾缓冲液(0 .0 5 mol/ L,p H为 2 .86 ) =5∶ 18(v/ v)为流动相 ,以乳酸司帕沙星为内标 ,流速 1.0 ml/ min,柱温为 2 0℃ ,紫外检测波长 2 32 nm,用螺旋霉素与内标的峰面积比进行定量。线性范围 2 5～ 32 0 0μg/ L ,最低检测浓度为2 0μg/ L ,对 18名健康受试者单次口服 4 5 0万 u螺旋霉素片剂后的药代动力学进行研究。结果 :18名健康受试者的血药浓度数据经 3p97拟合 ,符合血管外给药一室模型 ,AU C0～ t为 (44 72 .0± 6 74 .3) μg· h/ L,Cmax为(16 14 .4± 2 98.2 ) μg/ L,Tmax为 (2 .75± 0 .31) h,T1 /2 ke为 (2 .6 4± 0 .70 ) h。结论 :该方法简便 ,稳定性好 ,噪音小 ,灵敏度和准确度高 ,能够满足人体内低浓度药物的测定及药代动力学研究的要求。

Objective: To develop a method for the determination of spiramycin (SPM Ⅰ) in human plasma and study the clinical pharmacokinetics. Methods: High performance liquid chromatography (HPLC) has been performed on C 18 column with acetonitrile-0.05mol/L phosphatic buffer (pH=2.86, 5∶18 v/v) as the mobile phase. Detection wavelength was UV232nm. The standard curve of spiramycin was linear in the range of 25～3200μg/L. The minimum detection concentration was 20μg/L. This assay procedure has been applied to monitoring plasma levels of spiramycin in 18 healthy volunteers who reveived po administration of drug (450u spiramycin). Results: The drug concentration time profile conformed to the one compartment model . The AUC 0～t was (4472.0±674.3)μg·h/L and the C max was (1614.4±298.2)μg/L, T max (2.75± 0.31)h and T 1/2ke was (2.64±0.70)h, respectively. Conclusion: The study will provide a simple method for the determination of the plasma levels of spiramycin.