HPLC法测定血浆中头孢丙烯浓度及其人体药动学研究

Determination of Plasma Level of Cefprozil by HPLC and Its Pharmacokinetics in Human Body

目的:建立测定人血浆中头孢丙烯(CFPZ)浓度的高效液相色谱法,并应用于人体药动学研究。方法:10名男性健康受试者单次空腹口服CFPZ片500mg,采用高效液相色谱法测定CFPZ的血药浓度,色谱柱为KromasilKR100-5C18,流动相为0·01mol·L-1KH2PO4水溶液-乙腈(100:9·5),检测波长为254nm,柱温为室温,流速为1·0mL·min-1,进样量为20μL。结果:CFPZ血药浓度在0·25～15μg·mL-1范围内线性关系良好(r=0·9999),最低检测浓度为0·25μg·mL-1;低、中、高(0·25、0·5、2·5μg·mL-1)3种浓度(n=5)的日内RSD分别为4·8%、3·5%、1·3%,日间RSD分别为12·6%、6·7%、1·6%,相对回收率分别为97·7%、102·5%、103·6%,绝对回收率分别为88·5%、87·8%、85·3%。受试者单次空腹口服CFPZ片500mg后的Cmax为(8·66±1·57)mg·L-1,tmax为(1·85±0·8)h,t1/2为(1·4±0·18)h,AUC0～10为(28·28±3·28)mg·h·L-1,AUC0～∞为(29·43±3·54)mg·h·L-1。结论:CFPZ片体内过程符合血管外二室模型,口服后吸收迅速。本方法准确、灵敏、简便、特异性强、重现性好,适合于临床药动学研究。

OBJECTIVE： To establish an HPLC method for the determination of the plasma concentration of cefprozil （CFPZ） and the study of pharmacokinetics of CFPZ. METHODS： A total of 10 healthy male volunteers received a single oral dose of 500 mg tablets of cefprozil on empty stomach. The plasma concentration of cefprozil was determined by HPLC; in which the chromatographic column was Kromasil KR100- 5C18, and the mobile phase was 0.01mol·L^-1KH2PO4 aq. sol. - acetonitrile （100 ： 9.5） at a flow rate of 1.0 mL·min^-1; the detective wavelength was 254 nm; the column temperature was room temperature and the sample size was 20μL. RESULTS： The calibration curves of CFPZ were linear in the range of 0.25-15 μg·mL^-1 （r=0. 999 9） with a quantitation limit of 0.25 μg·mL^-1. The intra- day RSD of CFPZ （0.25, 0.5, 2.5 μg·mL^-1） were 4.8%, 3.5% and 1.3%, respectively; and the inter-day RSD were 12.6%, 6.7% and 1.6%, respectively. The relative recoveries were 97.7%, 102.5% and 103.6%, respectively; and the absolute recoveries were 88.5%, 87.8% and 85.3%, respectively. The pharmacokinetic parameters of 500 mg of CFPZ tablets were as follows： Cmax was （8.66±1.57）mg·L^-1; tmax was （1.85±0.8）h; t1/2 was （1.4±0.18）h; AUC0-10 was （28.28±3.28）mg·h·L^-1 and AUC0-∞ was （29.43±3.54）mg·h·L^-1. CONCLUSION： The physiological disposition of Cefprozil fitted two compartment model and it can be rapidly absorbed after oral administration. The method is sensitive, simple, specific and reproducible, and can be applied to the pharmacokinetic study.