Quantification of the HIV-integrase inhibitor raltegravir (MK-0518) in human plasma by high-performance liquid chromatography with fluorescence detection

Poirier, Jean‐Marie; Robidou, Pascal; Jaillon, Patrice

doi:10.1016/j.jchromb.2008.03.026

Cited by 28 publications

(24 citation statements)

References 11 publications

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“…RAL exhibited excitation and emission maxima at 310 and 410 nm, respectively. These maxima for RAL matched a previous report (30). The excitation and emission maxima for MK-0536 were 350 and 455 nm, respectively.…”

Section: Purification Of Rsv In-recombinantsupporting

confidence: 90%

Rous Sarcoma Virus Synaptic Complex Capable of Concerted Integration Is Kinetically Trapped by Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors

Pandey

Bera

Korolev

et al. 2014

Journal of Biological Chemistry

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Background: Structure of the three-domain Rous sarcoma virus integrase with viral DNA is lacking. Results: Soluble (Ͼ1.5 mg/ml) and stable synaptic complex using Rous sarcoma virus integrase, DNA, and HIV-1 strand transfer inhibitors was produced. Conclusion: Two integrase dimers assemble onto viral DNA to produce a synaptic complex. Significance: This is the first report producing a high concentration of soluble and kinetically stabilized RSV synaptic complex.

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Section: Purification Of Rsv In-recombinantsupporting

confidence: 90%

Rous Sarcoma Virus Synaptic Complex Capable of Concerted Integration Is Kinetically Trapped by Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors

Pandey

Bera

Korolev

et al. 2014

Journal of Biological Chemistry

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“…Raltegravir concentrations in plasma were determined by high-performance liquid chromatography (HPLC) with a fluorescence detector (Multifluorescence detector 2475; Waters), according to the method described by Poirier et al (17). Briefly, chromatographic separation was performed on a Sunfire C 18 column (particle size, 5 m; 4.6 by 150 mm; Waters).…”

Section: Methodsmentioning

confidence: 99%

Plasma and Intracellular (Peripheral Blood Mononuclear Cells) Pharmacokinetics of Once-Daily Raltegravir (800 Milligrams) in HIV-Infected Patients

Moltó

Valle

Back

et al. 2011

Antimicrob Agents Chemother

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The aim of this study was to evaluate the plasma and intracellular pharmacokinetics of raltegravir in HIV-infected patients receiving once-daily raltegravir. Five HIV-infected patients on stable therapy with lopinavir-ritonavir monotherapy whose HIV-1 RNA load was <50 copies/ml were included in this open-label, pilot study. Raltegravir was added to the antiretroviral regimen at a dose of 800 mg once daily from days 0 to 10. On day 10, a full pharmacokinetic profile was obtained for each participant. Raltegravir concentrations in plasma and peripheral blood mononuclear cells (PBMCs) were determined by high-performance liquid chromatography with a fluorescence detector and by liquid chromatography-tandem mass spectrometry (LC-MS/ MS), respectively. The values of the raltegravir pharmacokinetic parameters in plasma and PBMCs were calculated by noncompartmental analysis. Raltegravir was well tolerated, and all participants completed the study. No differences in the times to the maximum concentration of raltegravir in plasma or the raltegravir half-lives were observed between plasma and PBMCs. The geometric mean raltegravir maximum concentration, the concentration at the end of the dosing interval, and the area under the concentration-time curve during the dose interval in plasma versus PBMCs were 2,640 ng/ml (range, 887 to 10,605 ng/ml) versus 199 ng/ml (range, 82 to 857 ng/ml) (geometric mean ratio [GMR], 13.30; 95% confidence interval [CI], 3.11 to 56.89; P ‫؍‬ 0.003); 89 ng/ml (range, 51 to 200 ng/ml) versus 7 ng/ml (range, 2 to 15 ng/ml) (GMR, 13.21; 95% CI, 3.94 to 44.26; P ‫؍‬ 0.001); and 12,200 ng ⅐ h/ml (range, 5,152 to 30,130 ng ⅐ h/ml) versus 909 ng ⅐ h/ml (range, 499 to 2,189 ng ⅐ h/ml) (GMR, 13.43; 95% CI, 5.13 to 35.16; P < 0.001), respectively. Raltegravir does not accumulate in PBMCs, with intracellular concentrations being about 1/10 of the concentrations in plasma. Despite once-daily dosing, mean raltegravir concentrations at the end of the dosing interval in plasma and PBMCs exceeded the reported protein-binding-adjusted 95% inhibitory concentration (IC 95 ) and IC 50 for wild-type viral strains, respectively.

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“…21) Our's and Poirier's methods can specifically determine the raltegravir concentration and the sensitivities seem almost equivalent. Therefore, an alternative use is possible according to the availability of the equipments.…”

Section: Discussionmentioning

confidence: 97%

A Conventional LC-MS Method Developed for the Determination of Plasma Raltegravir Concentrations

Takahashi

Konishi

Kudaka

et al. 2008

Biological & Pharmaceutical Bulletin

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Raltegravir belongs to a new class of antiretrovirals acting for a human immunodeficiency virus (HIV)-1 integrase inhibition. Clinical trials of this drug have demonstrated potent antiviral activity in both therapy naïve and experienced patients. Thus, raltegravir has become an important component of combination treatment regimens used to treat patients with multidrug-resistant HIV-1. The quantification of raltegravir in human plasma is important to support clinical studies and determine pharmacokinetic parameters of raltegravir in HIV-1 infected patients. Recently, the LC-MS/MS superfine system was developed to determine plasma concentration of raltegravir; however, the system needs to be delicately set and the equipment is very expensive. Therefore, we developed a conventional LC-MS method to overcome these difficulties. Subsequently the method was validated by estimating the precision and accuracy for inter-and intraday analysis in the concentration range of 0.010-7.680 m mg/ml. The calibration curve was linear in this range. Average accuracy ranged from 97.2 to 103.4%. Relative standard deviations of both inter-and intraday assays were less than 10.4%. Recovery of raltegravir was more than 80.6%. This novel LC-MS method is accurate and precise enough to determine raltegravir levels in human plasma samples.

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Quantification of the HIV-integrase inhibitor raltegravir (MK-0518) in human plasma by high-performance liquid chromatography with fluorescence detection

Cited by 28 publications

References 11 publications

Rous Sarcoma Virus Synaptic Complex Capable of Concerted Integration Is Kinetically Trapped by Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors

Rous Sarcoma Virus Synaptic Complex Capable of Concerted Integration Is Kinetically Trapped by Human Immunodeficiency Virus Integrase Strand Transfer Inhibitors

Plasma and Intracellular (Peripheral Blood Mononuclear Cells) Pharmacokinetics of Once-Daily Raltegravir (800 Milligrams) in HIV-Infected Patients

A Conventional LC-MS Method Developed for the Determination of Plasma Raltegravir Concentrations

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