The development and application of a novel LC–MS/MS method for the measurement of Dolutegravir, Elvitegravir and Cobicistat in human plasma

Penchala, Sujan Dilly; Fawcett, Sandra; Else, Laura; Egan, Deirdre; Amara, Alieu; Elliot, Emilie R; Challenger, Elizabeth; Back, David; Boffito, Marta; Khoo, Saye

doi:10.1016/j.jchromb.2016.05.040

Cited by 31 publications

(26 citation statements)

References 10 publications

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“…A simple analytical method to quantitate drugs with small sample volume is highly desirable, that make it cost effective and socio-economically acceptable method. Several assays have been reported for the quantification of TFV, FTC, EVG, and RPV as an individual assay/combinations of these drugs in plasma (Aouri et al, 2013, Delahunty et al, 2009, Gomes et al, 2008, Illamola et al, 2016, Parsons & Marzinke, 2016, Penchala et al, 2016, & Prathipati et al, 2016). Since plasma processing is tedious, time-consuming and requires high sample volume, dried blood spot methodology is advantageous (Li & Tse, 2010).…”

Section: Introductionmentioning

confidence: 99%

LC–MS/MS method for the simultaneous determination of tenofovir, emtricitabine, elvitegravir and rilpivirine in dried blood spots

Prathipati

Mandal

Destache

2018

Biomedical Chromatography

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A simple, short, and rugged LC-MS/MS method for the simultaneous determination of tenofovir, emtricitabine, elvitegravir and rilpivirine was developed and validated. Dried blood spots were prepared with 25 μL of spiked whole blood. A 3 mm punch was extracted with methanol containing labeled internal standards. Ten microliters was injected into the LC-MS/MS using isocratic mobile phase composed of 0.1% formic acid in water and 0.1% formic acid in acetonitrile (45: 55 v/v) at a flow rate of 0.25 mL/min. The method was validated in the range of 10-2000 ng/mL for all four analytes. The intra-assay accuracy (RE) of the method was -4.73-4.78, 1.35-2.89, -8.89 to -0.49 and - 1.40-1.81 for tenofovir, emtricitabine, elvitegravir and rilpivirine, respectively. The inter-assay accuracy was within ±15% of nominal and precision (CV) was <15%. The hematocrit effect on quantification was nonsignificant at the tested hematocrit levels (35-70%). The dried blood spot method showed good agreement with the plasma method, and hence can be used as an alternative to plasma method.

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Section: Introductionmentioning

confidence: 99%

LC–MS/MS method for the simultaneous determination of tenofovir, emtricitabine, elvitegravir and rilpivirine in dried blood spots

Prathipati

Mandal

Destache

2018

Biomedical Chromatography

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“…Djerada et al, 2013;Grégoire et al, 2014;Penchala et al, 2016;Simiele et al, 2017;Tsuchiya et al, 2018). Djerada et al, 2013;Grégoire et al, 2014;Penchala et al, 2016;Simiele et al, 2017;Tsuchiya et al, 2018).…”

Section: Patients Sample Analysisunclassified

“…Therapeutic drug monitoring of antiretroviral drugs is useful in clinical scenarios where drug concentrations may be difficult to predict (NIH, n.d.). Currently only liquid chromatography-mass spectrometry (LC-MS) methods are available for determination of EVG in plasma (Aouri et al, 2013;Djerada et al, 2013;Penchala et al, 2016;Simiele et al, 2017;Tsuchiya et al, 2018). The aim of this work was to develop and validate a HPLC-UV method to measure EVG and the others new antiretrovirals DTG and RPV in human plasma.…”

Section: Introductionmentioning

confidence: 99%

Development and validation of an HPLC‐UV method for quantification of elvitegravir and two other new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV‐positive patients

Tempestilli

Ammassari

D’Avolio

et al. 2018

Biomedical Chromatography

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Therapeutic drug monitoring may be crucial in selected clinical conditions for the management of HIV infection. In recent years, new antiretrovirals have been introduced and in particular elvitegravir (EVG) is now recommended for first-line and simplification treatment as well as dolutegravir (DTG) and rilpivirine (RPV). The aim of this study was to develop and validate a high-performance liquid chromatography-ultraviolet (HPLC-UV) method for determining EVG and new antiretrovirals DTG and RPV in human plasma. Solid-phase extraction was applied to a 600 μL plasma sample. Chromatographic separation of the three drugs and internal standard was achieved with a gradient of acetonitrile and phosphate buffer on a C reverse-phase analytical column with a 20 min analytical run time. EVG and DTG were detected at 265 nm and RPV at 290 nm. Mean intra- and inter-day precisions were < 10%; the mean accuracy was <15%. Extraction recovery ranged between 105 and 82% for the drugs analyzed. Calibration curves were optimized according to the expected ranges of drug concentrations in patients; the coefficient of determination was >0.997 for all drugs. This method allows for monitoring EVG, DTG and RPV in the plasma of HIV-positive patients using HPLC-UV.

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“…Previously, EVG has been quantified in human biological matrixes such as plasma , seminal plasma , and peripheral blood mononuclear cells , as well as mouse plasma and tissue using LC–MS. A recent report has described the measurement of the integrase inhibitors raltegravir, dolutegravir, and EVG in human plasma and CSF .…”

Section: Introductionmentioning

confidence: 99%

“…Previously, EVG has been quantified in human biological matrixes such as plasma [4][5][6][7][8][9], seminal plasma [10,11], and peripheral blood mononuclear cells [12], as well as mouse plasma and tissue [13] using LC-MS. A recent report has described the measurement of the integrase inhibitors raltegravir, dolutegravir, and EVG in human plasma and CSF [14]. The assay had a calibration range of 5-1500 ng/mL in plasma and 1-200 ng/mL in CSF, which is not ideal considering the average trough concentrations of EVG in plasma at steady state is typically 409 ng/mL while the Cmax concentrations are 2500 ng/mL [15].…”

Section: Introductionmentioning

confidence: 99%

Development and validation of a UHPLC–MS/MS assay for elvitegravir measurement in human plasma and cerebrospinal fluid

Ocque

Hagler

Lapham

et al. 2018

Separation Science Plus

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The quantification of the integrase inhibitor, elvitegravir, in cerebrospinal fluid will significantly help understand its effects in the central nervous system. An ultra high performance liquid chromatography with tandem mass spectrometry method was successfully validated to measure elvitegravir in human plasma and cerebrospinal fluid. The biological fluid was diluted with methanol and the clear supernatant was injected into the chromatography system. The calibration was linear from 10.0 to 5000 ng/mL in plasma and 1.00 to 25 ng/mL in cerebrospinal fluid. Inter‐day and intra‐day variability ranged from 1.46 to 8.34% and accuracy ranged from –8.36 to 7.50% for quality controls in either plasma or cerebrospinal fluid analysis. The method was then applied to the measurement of elvitegravir concentrations in plasma and cerebrospinal fluid samples from an HIV+ patient enrolled in a clinical study who switched medications of Stribild® to Genvoya®. The validated method is suitable for the quantification of elvitegravir in plasma and cerebrospinal fluid.

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The development and application of a novel LC–MS/MS method for the measurement of Dolutegravir, Elvitegravir and Cobicistat in human plasma

Cited by 31 publications

References 10 publications

LC–MS/MS method for the simultaneous determination of tenofovir, emtricitabine, elvitegravir and rilpivirine in dried blood spots

LC–MS/MS method for the simultaneous determination of tenofovir, emtricitabine, elvitegravir and rilpivirine in dried blood spots

Development and validation of an HPLC‐UV method for quantification of elvitegravir and two other new antiretrovirals, dolutegravir and rilpivirine, in the plasma of HIV‐positive patients

Development and validation of a UHPLC–MS/MS assay for elvitegravir measurement in human plasma and cerebrospinal fluid

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