Quantification of 8 HIV-Protease Inhibitors and 2 Nonnucleoside Reverse Transcriptase Inhibitors by Ultra-Performance Liquid Chromatography with Diode Array Detection

Elens, Laure; Vériter, Sophie; Fazio, Vincent Di; Vanbinst, Roger; Boesmans, Daniel; Wallemacq, Pierre; Haufroid, Vincent

doi:10.1373/clinchem.2008.108647

Cited by 21 publications

(22 citation statements)

References 21 publications

(29 reference statements)

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“…The retention time of the internal standard was 2.996 min. The total run time was 9.5 min, shorter than the 14 min described by Elens et al 20 in the only previously published UPLC assay for anti-HIV drugs. The longer chromatographic analysis of Elens et al 20 included the measurement of the late eluting protease inhibitor tipranavir, which was not present in our assay because this drug is not registered in Brazil, being excluded of the recommended therapeutic schemes of the Brazilian Ministry of Health.…”

Section: Chromatography and Sample Preparationmentioning

confidence: 73%

“…The longer chromatographic analysis of Elens et al 20 included the measurement of the late eluting protease inhibitor tipranavir, which was not present in our assay because this drug is not registered in Brazil, being excluded of the recommended therapeutic schemes of the Brazilian Ministry of Health. 23,24 However, the retention times of Elens et al 20 were higher for all drug common for both assays: 4.844 for nevirapine, 8.033 for indinavir, 9.479 for amprenavir, 9.506 for saquinavir, 10.287 for atazanavir, 10.502 for efavirenz, 10.880 for lopinavir and 10.887 for ritonavir, with only partial resolution of these two analytes. Moreover, these authors employed an internal standard not commercially available, what reduces the practical application of the method.…”

Section: Chromatography and Sample Preparationmentioning

confidence: 99%

“…Besides this advantages, the need of complete chromatographic separation of all compounds been measured usually determines long analytical runs, leading to low throughput and high consumption of solvents, and by consequence a considerably production of chemical waste. An alternative to conventional HPLC methods is ultra-performance liquid chromatography (UPLC) that could render faster and highly resolutive separations, keeping the advantages and robustness of UV detection modes, as has been described by Elens et al 20 for the measurement of anti-HIV drugs. In the present work we describe a novel validated UPLC assay, with the use of a photodiode array detector, for the measurement of the following anti-HIV drugs in human plasma: nevirapine, indinavir, amprenavir, saquinavir, atazanavir, ritonavir, efavirenz and lopinavir.…”

Section: Introductionmentioning

confidence: 99%

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Ultra-performance liquid chromatographic method for simultaneous quantification of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors in human plasma

Antunes¹,

Poeta²,

Ribeiro³

et al. 2011

J. Braz. Chem. Soc.

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Um método rápido para a determinação de seis inibidores de protease (indinavir, amprenavir, saquinavir, atazanavir, lopinavir e ritonavir) e de dois inibidores não-nucleosídicos da transcriptase reversa (efavirenz e nevirapine), empregando cromatografia líquida de ultra-eficiência com detector de arranjo de diodos foi desenvolvido e validado. Após extração liquido-líquido de 0,5 mL de plasma com metil-tert-butil éter, os analitos foram separados em uma coluna ACQUITY UPLC BEH ® C18 (2,1 × 150 mm, d.p. 1,7 µm), eluída com um gradiente de tampão fosfato trietilamônio pH 3.0 e acetonitrila. O tempo total de análise cromatográfica foi de 9,5 min. As curvas de calibração foram lineares entre 0,1 a 10,0 µg mL -1. O limite inferior de quantificação foi 0,1 µg mL -1 para todos os fármacos. A exatidão esteve entre 94,9 e 103,5%. Os coeficientes de variação intra e inter-dias foram inferiores a 7,7% para todos os analitos. Os rendimentos de extração foram superiores a 88,2%.A fast ultra-performance liquid chromatographic with diode-array detection method has been developed and validated for the determination of six protease inhibitors (indinavir, amprenavir, saquinavir, atazanavir, lopinavir, and ritonavir) and two non-nucleoside reverse transcriptase inhibitors (efavirenz and nevirapine). After liquid-liquid extraction of 0.5 mL plasma with methyl-tert-butyl ether, the analytes were separated on a ACQUITY UPLC BEH ® C18 column (2.1 × 150 mm, p.d. 1.7 µm) column eluted with a gradient of acetonitrile and triethylammonium phosphate buffer 5 mmol L -1 pH 3.0. The total run time was 9.5 min. Calibration curves were linear in the range 0.1 to to 10.0 µg mL -1. The lower limit of quantitation was 0.1 µg mL -1 for all drugs. Accuracy ranged from 94.9 to 103.5%. Both interday and intraday coefficients of variation were less than 7.7% for all analytes. The extraction yields were greater than 88.2%. Keywords: antiretroviral drugs, ultra-performance liquid chromatography, therapeutic drug monitoring, UPLC-DAD IntroductionAntiretroviral therapy for human immunodeficiency virus (HIV) infections usually consists of combinations of nucleoside reverse transcriptase inhibitors (NRTIs), non-nucleoside reverse transcriptase inhibitors (NNRTIs), protease inhibitors (PIs) and, more recently, entry inhibitors and integrase inhibitors. 1 The currently approach to the therapy of HIV infection is the so-called "highly active antiretroviral therapy" (HAART), which is based on the combination of several drugs in the daily dosing regimen. The usual HAART scheme consists of one or more NRTIs, one or more PIs and one NNRTI.2 Several reports had demonstrated the relationship between plasma drug concentrations and clinical effects, either toxicity or efficacy, for compounds of the NNRTI and PI groups. [3][4][5][6][7][8] Therefore, these drugs are prone for therapeutic drug monitoring (TDM) programs and, considering the necessity of interlaboratory comparison of results for the use of consensual therapeutic target levels, reliable analytical methods mu...

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Section: Chromatography and Sample Preparationmentioning

confidence: 73%

Section: Chromatography and Sample Preparationmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Ultra-performance liquid chromatographic method for simultaneous quantification of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors in human plasma

Antunes¹,

Poeta²,

Ribeiro³

et al. 2011

J. Braz. Chem. Soc.

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“…Several LC-MS/MS methods described in the literature were developed for simultaneous quantification of various anti-HIV agents with a long analytical time. 16,24,26,27,29,43 This method for quantitation of efavirenz in human plasma show an analytical time of 2.0 min and was successfully applied in a bioequivalence study. The use of mass spectrometric detection in MRM mode is less demanding on chromatographic separation between analytes and early-eluting interferents due to improved selectivity and this feature can be explored to increase sample throughput by reducing sample analysis time, provided adequate selectivity without ion suppression is achieved.…”

Section: Discussionmentioning

confidence: 99%

A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

Bedor¹,

Filho²,

Ramos³

et al. 2011

Quím. Nova

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Recebido em 12/7/10; aceito em 17/12/10; publicado na web em 25/3/11An LC-MS/MS method has been developed for the determination of efavirenz (EFZ) in human plasma using hydrochlorothiazide as internal standard (I.S.). An ESI negative mode with multiple reaction-monitoring was used monitoring the transitions m/z 313.88→69.24 (EFZ) and 296.02→204.76 (I.S.). Samples were extracted using liquid-liquid extraction. The total run time was 2.0 min. The separation was achieved with HPLC-RP using a monolithic column. The assay was linear in the concentration range of 100 -5000 ng mL -1 . The mean recovery was 83%. Intra-and inter-day precision were < 9.5% and < 8.9%, respectively and accuracy was in the range ± 8.33%. The method was successfully applied to a bioequivalence study.

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“…There are several methods described in the literature for the quantitative analysis of atazanavir in plasma, either alone [5][6][7] or in combination with other ARVs [7][8][9][10]. Some authors reported the use of mass spectrometry for detection [10], which is not routinely available in all laboratories.…”

Section: Introductionmentioning

confidence: 99%

Liquid Chromatographic Assay for the Analysis of Atazanavir in Rat Plasma after Oral Administration: Application to a Pharmacokinetic Study

Singh¹

2014

J Chromat Separation Techniq

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A new reverse phase liquid chromatographic method for the investigation of atazanavir in rat plasma was developed after oral administration. The chromatographic separation was achieved on Phenomenex C 18 column (250 mm × 4.6 mm I.D., 5 μm), under isocratic conditions using UV detection at 249 nm. The optimized mobile phase consisted of a mixture of potassium dihydrogen phosphate (pH 3.5) and acetonitrile (58: 42, v/v) at a flow rate of 1ml/min. The system was found to produce sharp and well-resolved peak for atazanavir with retention time of 5.78 min. The linear regression analysis for the calibration curves showed a good linear correlation over the concentration range 0.050-2.0 μg/ml, with determination coefficients, R 2 , exceeding 0.9989. The limits of detection (LOD) and quantitation (LOQ) were found to be 0.004 μg/ml and 0.012 μg/ml, respectively. The method was successfully applied for the pharmacokinetic in rats. Atazanavir concentration in plasma reached (C max ) was 0.087 μg/ml at 3 h after oral administration of 7.2 mg/kg/rat. The AUC 0-12 was 0.4812 μg/ml*h and the apparent plasma half-life (t 1/2 ) was 7.5 h. This method was found to be suitable for examining atazanavir concentration in rats, after oral administration of atazanavir in a single dose.

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Quantification of 8 HIV-Protease Inhibitors and 2 Nonnucleoside Reverse Transcriptase Inhibitors by Ultra-Performance Liquid Chromatography with Diode Array Detection

Cited by 21 publications

References 21 publications

Ultra-performance liquid chromatographic method for simultaneous quantification of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors in human plasma

Ultra-performance liquid chromatographic method for simultaneous quantification of HIV non-nucleoside reverse transcriptase inhibitors and protease inhibitors in human plasma

A sensitive and robust lc-ms/ms method with monolithic column and electrospray ionization for the quantitation of efavirenz in human plasma: application to a bioequivalence study

Liquid Chromatographic Assay for the Analysis of Atazanavir in Rat Plasma after Oral Administration: Application to a Pharmacokinetic Study

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