高效液相色谱法测定人血浆中氟康唑浓度及其的应用.docVIP

高效液相色谱法测定人血浆中氟康唑浓度及其的应用 　　[摘要] 目的:建立测定人血浆中氟康唑浓度的RP-HPLC法,并应用于临床药代动力学研究。方法:采用二氯甲烷萃取,高效液相色谱法检测,以单硝酸异山梨酯为内标,Phenomenx C18色谱柱(4.6 mm×250 mm,4 μm),流动相为乙腈-水-冰醋酸(25∶75∶0.2),流速为1.0 ml/min;检测波长为261 nm。结果:血浆中内源性物质不干扰氟康唑的检测,氟康唑的线性范围为0.125～8.000 μg/ml,批内、批间精密度均小于15%,低、中、高浓度的(0.25 μg/ml、1 μg/ml和4 μg/ml)平均提取回收率分别为100.0%、98.8%、86.7%。结论:该法操作快速、简单、准确,符合生物样品检测要求,可用于临床药代动力学研究中大批量血样的处理。 　　[关键词] 氟康唑;高效液相色谱;药代动力学 　　[中图分类号] R92[文献标识码]C [文章编号]1673-7210(2009)08(b)-037-03 　　 　　Determination of the concentration of fluconazol in healthy volunteer human plasma by RP-HPLC and applied in clinical pharmacokinetics 　　YE Chixia, FANG Jing, ZHOU Xueqin 　　(Department of Pharmacy, Shenzhen Hospital of Peking University, Shenzhen 518036,China) 　　[Abstract] Objective: To establish a method for determining the concentration of fluconazol in human plasma. Methods: The Phenomenex C18 column(4.6 mm×250 mm, 4 mm) was used. The mobile phase was consisted of water, acetonitrile and glacial acetic acid (25∶75∶0.2), the flow rate was 1.0 ml/min and the detection wavelength was set at 261 nm. Results: The linear ranges of fluconazol was 0.125-8.000 μg/ml, The intra and inter day precision over the entire concentration range were less than 15%. The average recoveries were 100.0%, 98.8% and 86.7% respectively according to the low, middle, high concentrations(0.25 μg/ml, 1 μg/ml, 4 μg/ml). Conclusion: The method is fast, reliable, accurate and can be used for mass hematoid treatment in clinical pharmacokinetics. 　　[Key words] Fluconazol; High performance liquid chromatography (HPLC); Pharmacokinetics 　　 　　氟康唑(fluconazol)为三唑类广谱抗真菌药,通过高度选择性抑制真菌羊毛甾醇14α-脱甲基酶及真菌细胞内细胞色素P450的羟化反应,从而抑制真菌细胞膜上麦角固醇的生物合成,破坏真菌细胞壁的完整性,抑制真菌的生长繁殖。同时还能抑制细胞色素氧化酶与过氧化物酶,使真菌细胞内过氧化物大量积聚造成真菌死亡。其口服吸收快、体内分布广、半衰期长、耐受性好、副作用小,临床广泛用于各种深部真菌感染性疾病及浅表、黏膜真菌感染的治疗。本文通过建立高效液相色谱法来测定人血浆中氟康唑血药浓度,并用于健康人体药代动力学的研究,以为临床血药浓度的监控及合理调整给药剂量提供依据。 　　1 仪器和试药 　　1.1 仪器 　　LC-10ATvp高效液相色谱仪,SPD-10Avp紫外检测器,LC-10ATvp输液泵,均为日本岛津公司生产;N2000色谱数据工作台软件(浙江大学智达信息工程有限公司);AT-130柱温箱(AUTO