摘要
目的建立高效液相色谱法测定人血浆中那格列奈浓度的方法，研究那格列奈胶囊和片剂的药物动力学及生物等效性。方法以迪马C18（250mm×1．5mm，5μm）为分析柱，乙腈-0．02mol·L^-1乙酸胺缓冲液（40：60）为流动相，流速为1．0mL·min^-1，紫外检测波长为214nm，柱温为40℃，瑞格列奈为内标，测定人血浆中那格列奈的浓度。结果在浓度0．1875～12μg·mL^-1，那格列奈和内标峰面积比值与浓度呈良好的线性关系（r2=0．99547），最小检出浓度为0．09375μg·mL^-1。那格列奈的平均回收率为103％±7％，日内、日间RSD均≤6．8％，那格列奈体内过程符合二室模型，tmax、Cmax、t1／2β、AUC0～∞h分别为（1．36±0．40）h、（6．42±0．30）μg·mL^-1、（1．36±2．26）h、（16．10±1．54）μg·h·mL^-1。结论本方法简便、灵敏、准确，可用于那格列奈血药浓度检测和药物动力学研究。经统计学分析，试验制剂（胶囊剂）和参比制剂（片剂）具有生物等效性。
OBJECTIVE To establish an HPLC method to determine the concentration of nateglinide in the human plasma and to study its pharmacokinetics, relative bioequivalence of nateglinide capsules and tablets in 18 healthy volunteers. METHODS A single oral dose of 90 mg nateglinide capsules or tablets was given to healthy volunteers in an open randomized two-way cross-over design. The separation was performed on a Diamonsil C18 column （250 mm×1.5 mm, 5μm）. The mobile phase was composed of acetonitril-0. 02 mol · L^-1 （40： 60）. And the column temperature was 40℃ with the flow rate was 1.0mL·min^-1. The detection wavelength was 214 nm. RESULTS The calibration curve of nateglinide was linear within 0. 187 5～12 μg·mL^-1 （r^2 =0. 995 47）, and the validated limit of quantitation was 0. 093 75μg·mL^-1. The average recovery was 103%±7%; the intra-day RSD and inter-day RSD were both lower than 6.8%. The pharmacokonetic parameters of nateglinide test preparation were as follows： tmax was （1.36±0.40） h, Cmax was （6. 42±0. 30） μg · mL^-1 , t1/2β was （1.36±2. 26） h, and AUG0-∞h was （16. 10±1.54） μg · h · mL^-1, which accorded with the two-compartment model. CONCLUSIONS This method is simple, accurate, reproducible, and suitable for the determination of concentration and pharmacokinetics of nateglinide. Statistical analysis showed that the reference preparation and the test preparation were bioequivalent.
出处
《中南药学》
CAS
2006年第5期343-345,共3页
Central South Pharmacy
