Validation of a fast method for quantitative analysis of elvitegravir, raltegravir, maraviroc, etravirine, tenofovir, boceprevir and 10 other antiretroviral agents in human plasma samples with a new UPLC-MS/MS technology

Djerada, Zoubir; Féliu, Catherine; Tournois, Claire; Vautier, Damien; Binet, Laurent; Robinet, Arnaud; Marty, Hélène; Gozalo, Claire; Lamiable, Denis; Millart, Hervé

doi:10.1016/j.jpba.2013.08.002

Cited by 64 publications

(74 citation statements)

References 22 publications

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“…This offers a higher extraction recovery rate of tenofovir of Ͼ93.93%. This value is significantly higher than the tenofovir extraction efficiency reported by Jung et al and Djerada et al (about 70%) (20,21).…”

Section: Discussioncontrasting

confidence: 60%

“…The LOQ of ATZ, RTV, and TFV has been improved by 2,500-fold, 100-fold, and 10-fold, respectively, compared to that reported by Jung et al (20). It also has been improved by 8,750-fold, 156-fold, and 12-fold, respectively, in a comparison with that in the study of Djerada et al (21).…”

Section: Discussionmentioning

confidence: 47%

“…However, in the study by Jung et al (20), the QC samples used for the recovery and matrix effects experiments were selected at two concentrations, 10 and 100 ng/ml, making the range of the assay narrow and not representative compared to the reported linearity range (1 to 500 ng/ml). In the research of Djerada et al (21), the concentrations of the QC samples were 63, 2,000, and 4,000 ng/ml for ATZ, 25, 200, and 400 ng/ml for TFV, and 25, 800, and 1,600 ng/ml for RTV. All of these may be too high to get an accurate and sensitive measurement of the low concentrations of drugs in biological samples.…”

Section: Discussionmentioning

confidence: 94%

“…Methods for the detection of antiretroviral agents mostly use LC-MS/MS, which can offer high sensitivity and selectivity, which are required for pharmacokinetic and therapeutic drug monitoring (TDM) studies. Two methods were previously described for the determination of Ͼ10 antiretroviral drugs for routine TDM (20,21). The simultaneous detection of different classes of antiretroviral drugs (including hydrophobic and hydrophilic compounds) can save labor, time, and sample volumes.…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

A Simple, Efficient, and Sensitive Method for Simultaneous Detection of Anti-HIV Drugs Atazanavir, Ritonavir, and Tenofovir by Use of Liquid Chromatography-Tandem Mass Spectrometry

Koehn

Ding

Freeling

et al. 2015

Antimicrob Agents Chemother

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In the treatment of HIV infection, a combination of anti-HIV drugs is commonly used in highly active antiretroviral therapy (HAART). One such combination recommended for clinical therapy consists of the two HIV protease inhibitors atazanavir and ritonavir and the HIV nucleotide reverse transcriptase inhibitor tenofovir. The detection of plasma and cell drug concentrations provides an assessment of actual drug exposure and patient compliance. We thus developed a simple, efficient, and sensitive method to simultaneously extract and detect these three drugs in plasma and peripheral blood mononuclear cells. The use of a liquid-liquid extraction followed by protein precipitation provided a simple process, yielding a high recovery rate for all three drugs in plasma (>92%) and in cells (>86%). The liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay was able to detect 0.01, 0.25, and 2.5 pg (2, 50, and 500 pg/ml, respectively) in 5 l for atazanavir, ritonavir, and tenofovir, respectively. Validation of the method exhibited high precision and accuracy. This method was subsequently applied to a primate study to determine the concentrations of all three drugs in both plasma and cell samples. This validated method can be useful for an evaluation of drug concentrations in biological samples in an efficient and sensitive manner. Since the introduction of highly active antiretroviral therapy (HAART) in the 1990s, the outcome in terms of life expectancy for people suffering from human immunodeficiency virus (HIV) has greatly improved due to the plasma virus load reduction to below-detectable levels (1, 2). ART treatment usually includes two or three anti-HIV drugs from different drug classes targeting different viral proteins in order to increase efficacy and lower the risk of the virus developing resistance to the treatment. A common drug combination is a nucleoside or nucleotide reverse transcriptase inhibitor (NRTI or NtRTI, respectively) with a nonnucleoside reverse transcriptase inhibitor (NNRTI) or with one or more protease inhibitors (PIs) (3).One of the first-line therapies recommended for ART-naive people is the combination of atazanavir (ATZ), ritonavir (RTV), and tenofovir (TFV) (3). ATZ is a commonly used PI that exhibits 10-to 100-fold higher antiviral potency than that of other PIs, including nelfinavir or indinavir, and demonstrates a lower rate of viral drug resistance (4-9). ATZ is typically used in combination with RTV, another PI, which inhibits the cytochrome P450 3A isoenzyme (CYP3A) metabolism of ATZ, thereby boosting ATZ exposure. RTV has also been shown to inhibit drug efflux transport by P-glycoprotein (PgP) and therefore might enhance the cellular retention of other PIs (10). TFV is a nucleotide reverse transcriptase inhibitor (NtRTI) clinically administered as tenofovir disoproxil fumarate (TDF), an oral prodrug that increases absorption and is readily hydrolyzed to the TFV active form (11). While a number of bioanalytical assays have been developed for the three drugs, they are often time...

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Section: Discussioncontrasting

confidence: 60%

Section: Discussionmentioning

confidence: 47%

Section: Discussionmentioning

confidence: 94%

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

A Simple, Efficient, and Sensitive Method for Simultaneous Detection of Anti-HIV Drugs Atazanavir, Ritonavir, and Tenofovir by Use of Liquid Chromatography-Tandem Mass Spectrometry

Koehn

Ding

Freeling

et al. 2015

Antimicrob Agents Chemother

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“…LC-MS/MS [13] have been developed and used for the simultaneous quantification of elvitegravir and ritonavir in rat plasma. UPLC-MS/MS simultaneous estimation method has been developed for quantification of elvitegravir with 15 other antiretroviral drugs in human plasma [14]. To illustrate plasma levels of elvitegravir with rilpivirine (RPV) in HIV patients, Aouri et al [15] reported a LC-MS/MS method with the stable isotopic labeled compounds RPV-13C6 and elvitegravir D5 as corresponding internal standards.…”

Section: Introductionmentioning

confidence: 99%

A Highly Sensitive and Rugged LC-MS/MS Method Development and Validation for Determination of Elvitegravir in Rat Plasma: Application to Pharmacokinetic Study

Adepu¹,

Kambhayatughar²,

Vedula³

2017

Asian J. Chem.

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A sensitive, rugged and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method is required for the reliable quantification of elvitegravir in rat pharmacokinetic samples. The objective of the current analytical work was to develop and validate LC-MS/MS method for the pharmacokinetic study after oral administration of elvitegravir in rats. The chromatographic separation was achieved isocratically using 5 mM ammonium formate (pH 3.0 ± 0.2): acetonitrile (30:70 v/v) on Phenomenex Luna 5 µ, C18 column (100 mm × 4.60 mm) with a flow rate and total run time of 0.6 mL/min and 4 min, respectively. The internal standard was elvitegravir D5. The linearity plots were analyzed by using 1/x 2 associated with a ten-point calibration standards. The range of concentration of elvtegravir for the method validation was 20.170 to 3428.942 ng/mL (r 2 ≥ 0.9976). The retention times of elvitegravir and elvitegravir D5 were 1.05 ± 0.015 min and 1.06 ± 0.015 min, respectively. The % recovery for analyte and internal standard was 80.84 ± 4.99 and 85.09 ± 3.45, respectively. The % mean stability for analyte was in the range of 97.84 to 105.31. The developed and systematically validated method was effectively implemented to the pharmacokinetic analysis of rat plasma samples following oral administration.

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Therapeutic drug monitoring of mitotane: Analytical assay and patient follow‐up

Féliu

Cazaubon

Guillemin

et al. 2017

Biomedical Chromatography

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Adrenocortical carcinoma (ACC) is an aggressive malignancy of the adrenal gland. Mitotane (o,p'-DDD) is the most effective chemotherapy for ACC. According to the literature, mitotane plasma trough concentrations within 14-20 mg L are correlated with a higher response rate with acceptable toxicity. Therapeutic drug monitoring (TDM) of mitotane is therefore recommended. The aim of this study was to propose a robust and simple method for mitotane quantification in plasma. The validation procedures were based on international guidelines. Sample preparation consisted of a single protein precipitation with methanol using 100 μL of plasma. The supernatant was submitted to liquid chromatography coupled with ultra-violet detection at 230 nm. Mitotane retention time was 7.1 min. The limit of detection was 0.1 mg L and the limit of quantification was 0.78 mg L . The assay demonstrated a linear range of 0.78-25 mg L with correlation coefficients (r ) at 0.999. Inter- and intra-assay precision was <4.85%. Evaluation of accuracy showed a deviation <13.69% from target concentration at each quality control level. This method proved easy and rapid to perform mitotane TDM and required a small volume of sample. It was successfully applied to routine TDM in our laboratory.

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Validation of a fast method for quantitative analysis of elvitegravir, raltegravir, maraviroc, etravirine, tenofovir, boceprevir and 10 other antiretroviral agents in human plasma samples with a new UPLC-MS/MS technology

Cited by 64 publications

References 22 publications

A Simple, Efficient, and Sensitive Method for Simultaneous Detection of Anti-HIV Drugs Atazanavir, Ritonavir, and Tenofovir by Use of Liquid Chromatography-Tandem Mass Spectrometry

A Simple, Efficient, and Sensitive Method for Simultaneous Detection of Anti-HIV Drugs Atazanavir, Ritonavir, and Tenofovir by Use of Liquid Chromatography-Tandem Mass Spectrometry

A Highly Sensitive and Rugged LC-MS/MS Method Development and Validation for Determination of Elvitegravir in Rat Plasma: Application to Pharmacokinetic Study

Therapeutic drug monitoring of mitotane: Analytical assay and patient follow‐up

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