RP-HPLC测定氟康唑血药浓度及其药动学和生物利用度

 目的：建立RP HPLC快速测定人血清中氟康唑(FCZ)浓度。研究该药物在人体内的药动学和生物利用度。方法：血样经碱化、乙酸乙酯提取后，在Spherisorb C₁₈(200 mm×4.0 mm，5μm)不锈钢柱上分离，流动相为乙腈-水-磷酸(250∶750∶1.2，以二乙胺调pH 4)，以氨苯蝶啶为内标，在260 nm处检测，所得血浓数据用Z89NLF程序进行模型嵌合，求出有关药动学参数。结果：FCZ血清浓度在0.25 μg·ml^-1～10.0 μg·ml^-1范围内线性良好，最低检出浓度为0.1 μg·ml^-1，日内及日间精密度分别为6.30%(n=5)和8.98%(n=5)，方法回收率为99.33%～102.28%。对8名健康志愿受试者单剂量po FCZ片剂150 mg后研究表明，其药时曲线符合零级吸收的开放一室模型，达峰时间t_max为1.69 h，血清峰浓度c_max为3.30 μg·ml^-1，消除半衰期t_1/2约为27 h。双单侧检验结果显示，FCZ片剂与进口胶囊剂生物等效，相对生物利用度F rel为108.32%。结论：本方法简便、准确，能较好地满足FCZ临床血药浓度监测及人体药动学研究。

The calcium absorption of two kinds of calcium carbonate plus vitamin D preparations in healthy volunteers

OBJECTIVE:To develop a sensitive RP-HPLC method for the determination of fluconazole (FCZ) in human serum and to study its pharmacokinetics and bioavailability in human. METHOD: The drug was alkalized and extracted with ethyl acetate from serum and separated from endogenous interference on a Spherisorb C₁₈(200 mm×4.0 mm, 5μm) column with acetonitrile water phosphoric acid (250∶750∶1.2, pH was adjusted to 4 by diethyl amine). UV detector was set at 260 nm and triamterene was used as the internal standard. The data obtained were analyzed with Z89NLF program. RESULTS: A linear relationship was obtained between the peak area ratio and the concentration of FCZ from 0.25 to 10.0 μg·ml^-1and the lowest limit of detection of FCZ in serum was 0.1 μg·ml^-1. Within run and between run precisions were 6.30% (n=5) and 8.98% (n=5), respectively. The recoveries were 99.33%～102.28%. The one compartment open model with zero order absorption was used to described the time course of serum concentrations of FCZ in eight human volunteers following administration of a single oral dose (150 mg) as tablets. The results were t_max=1.69 h, c_max=3.30 μg·ml^-1,t_1/2=27 h and Frel=108.32%. CONCLUSION: The method is simple and accurate and is very suitable for the study of FCZ pharmacokinetics. The tested tablets and the reference capsules is bioequivalent.