HPLC法测定人血浆中柳氮磺吡啶与磺胺吡啶浓度及其药动学研究

摘要

Objective To establish an HPLC method for the determination of sulfasalazine and sulfapyridine in human plasma and to study the pharmacokinetics in Chinese healthy volunteers following oral administration of sulfasalazine enteric-coated tablets. Methods In the study, 24 volunteers were administered with single oral dose of 500mg of sulfasalazine enteric-coated tablets. The plasma concentrations of sulfasalazine and sulfapyridine were determined by HPLC-UV method. The pharmacokinetic parameters were calculated with aid of the software DAS2.1.1. Results The calibration curve of sulfasalazine was linear in the range from 0.50 to 20.10μg/mL (r1=0.9991) and sulfapyridine was linear in the range from 0.10-4.01 μg/mL(r2=0.9968). The lower limit of quantification of sulfasalazine and sulfapyridine were 0.50μg/mL and 0.10μg/mL, respectively. Both the intra-day and inter-day RSD were less than 10%. The main pharmacokinetic parameters of sulfasalazine and sulfapyridine were as follows: t1/2 were(8.02±3.19) and (·12.88± 5.41)h, Cmax were (7.78 ± 3.43) and (2.48 ± 0.79)μg/mL, Tmax were (6.42±1.32) and (13.67±4.06)h, AUC(0~t)were (85.85±44.25) and (56.39 ± 25.13)μg·h/mL, respectively. Conclusion The HPLC-UV method was convenient, precise and reproducible. It can be used in the determination of sulfasalazine and sulfapyridine in human plasma and clinical pharmacokinetics studies.%目的 建立测定人血浆中柳氮磺吡啶和磺胺吡啶的高效液相色谱法,研究单剂量口服柳氮磺吡啶肠溶片在中国健康受试者体内的药动学特征.方法 24名健康受试者口服500mg柳氮磺吡啶肠溶片,采用HPLC-UV法测定血浆中柳氮磺吡啶及磺胺吡啶的浓度,利用DAS2.1.1软件计算药动学参数.结果 该方法中柳氮磺吡啶浓度在0.50～20.10μg/mL(r1=0.9991)、磺胺吡啶浓度在0.10～4.01 μg/mL(r2=0.9968)范围内呈线性关系,最低检测浓度分别为:0.50和0.l0μg/mL.日内、日间RSD均小于10％.单次口服给药后,药动学参数如下:柳氮磺吡啶及磺胺吡啶的fl/2分别(8.02±3.19)、(12.88±5.41)h,Cmax分别为(7.78±3.43)和(2.48±0.79)μg/mL；Tmax分别为(6.42±1.32)和(13.67±4.06)h；AUC(0～t)分别为(85.85±44.25)和(56.39±25.13)μg·h/mL.结论 此方法简便、准确、重现性好,可用于柳氮磺吡啶及磺胺吡啶的血药浓度测定及人体药动学研究.