Determination of indinavir, a HIV-1 protease inhibitor, in human plasma using ion-pair reversed-phase high-performance liquid chromatography.

Determination of indinavir, a HIV-1 protease inhibitor, in human plasma using ion-pair reversed-phase high-performance liquid chromatography.
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使用离子对反相高效液相色谱法测定人血浆中茚地那韦(一种 HIV-1 蛋白酶抑制剂)。

DOI:
10.1097/00007691-199906000-00021
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发表时间:
1999
影响因子:
2.5
通讯作者:
Raisys,VA
Raisys,VA
中科院分区:
医学3区
文献类型:
--
作者:
Li,W;Coombs,RW;Collier,AC;Raisys,VA

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茚地那韦被广泛用作治疗HIV-1感染的强效抗逆转录病毒疗法的组成部分。由于治疗的病毒学失败可能是由于药物水平低于治疗水平,因此监测茚地那韦水平在临床管理中可能很重要。我们已经开发了一种简单,准确,精密的高效液相色谱法(HPLC)测定人血浆中茚地那韦的浓度。在我们的方法中,茚地那韦用二氯甲烷在pH 10.4从血浆中提取,这导致茚地那韦和内标物(IS),甲基-茚地那韦的定量回收率(分别为86%和80%-97%)。使用Luna C18(2)(Phenomenex)分析柱完成色谱分离,移动的流动相由乙腈:磷酸盐缓冲液(25 mM)和0.2%三乙胺pH 7.0(34.5:65.5,v/v)组成。离子配对试剂三乙胺是必要的,以确保茚地那韦的适当保留时间,并区分它与其他蛋白酶抑制剂的共提取。在210 nm处进行定量。当提取1 mL血浆等分试样时,标准曲线在25- 5,000 ng/mL浓度范围内呈线性(r2> 0.999)。日间和日内变异系数可接受。该测定用于测定接受茚地那韦1200 mg每12小时、1000 mg每12小时或800 mg每8小时给药的12例受试者血浆中的谷和峰水平。本研究中测得的茚地那韦浓度(谷值26-768 ng/mL; 1 h时的峰值3,309 - 17,568 ng/mL)范围比先前定义的范围(谷值50-300 ng/mL;峰值6,000 - 12,000 ng/mL)更宽。本研究说明了茚地那韦监测的三种潜在用途:评估个体给药方案,评估患者依从性,以及监测由药物清除率变化引起的异常茚地那韦水平。
Indinavir is widely prescribed as a component of potent antiretroviral therapy for the treatment of HIV-1 infection. Because virologic failure of therapy can result from subtherapeutic drug levels, monitoring of indinavir levels may be important in clinical management. We have developed a simple, accurate, and precise high-performance liquid chromatographic (HPLC) assay for measurement of indinavir concentration in human plasma. In our method, indinavir was extracted from plasma with dichloromethane at pH 10.4, which resulted in quantitative recovery of indinavir and the internal standard (IS), methyl-indinavir (86% and 80%–97%, respectively). Chromatographic separation was accomplished using a Luna C18 (2)(Phenomenex) analytic column with a mobile phase composed of acetonitrile: phosphate buffer (25 mM) and 0.2% triethylamine pH 7.0 (34.5: 65.5, v/v). Ion-paired reagent triethylamine was necessary to ensure an appropriate retention time for indinavir and differentiate it from other protease inhibitors that were coextracted. Quantification was performed at 210 nm. The standard curves were linear (r 2> 0.999) over the concentration range 25–5,000 ng/mL, when 1-mL aliquots of plasma were extracted. Inter-and intraday coefficients of variation were acceptable. The assay was used to determine trough and peak levels of in plasma from 12 subjects who received indinavir 1200 mg every 12 hours, 1000 mg every 12 hours, or 800 mg every 8 hours. The concentrations of indinavir found in this study (trough 26–768 ng/mL; peak at 1 hr 3,309–17,568 ng/mL) has a wider range than defined previously (trough 50–300 ng/mL; peak 6,000–12,000 ng/mL). This study illustrates three potential uses of indinavir monitoring: to assess individual dosing regimen, to assess patient compliance, and to monitor unusual indinavir levels caused by changed drug clearance.
接受茚地那韦(一种 HIV 蛋白酶抑制剂)患者的门静脉血栓。
DOI: --
发表时间: 1997
期刊: AIDS (London)
影响因子: --
作者:
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茚地那韦相关肾结石的治疗。
DOI: --
发表时间: 1997
期刊: Journal of Urology
影响因子: 6.6
作者:
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DOI: 10.1056/nejm199709113371102
发表时间: 1997-09-11
影响因子: 158.5
作者:
Gulick, RM;Mellors, JW;Chodakewitz, JA
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晚期 HIV 感染患者中的茚地那韦相关性肝炎
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发表时间: 1998
影响因子: 1.4
作者:
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DOI: --
发表时间: 1995
期刊: Journal of chromatography. B, Biomedical applications
影响因子: --
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