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

Ocque, Andrew J.; Hagler, Colleen E.; Lapham, Jill; Morse, Gene D.; Letendre, Scott; Ma, Qing

doi:10.1002/sscp.201800043

Cited by 3 publications

(2 citation statements)

References 17 publications

(31 reference statements)

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“…The drug concentrations we used are based on previously reported plasma levels from human subjects, which were generally above 3 μM and below 10 μM, for both EVG and raltegravir (RAL) ( Gilead Sciences International Limited, 2013 ; Podany et al, 2017 ; Ocque et al, 2018 ; Tsuchiya et al, 2018 ; Yonemura et al, 2018 ). Plasma concentrations of antiretrovirals may represent the higher end of drug concentration at the site of action and are much higher than those reported in patient cerebrospinal fluid (CSF) samples.…”

Section: Methodsmentioning

confidence: 99%

Inhibition of lipid synthesis by the HIV integrase strand transfer inhibitor elvitegravir in primary rat oligodendrocyte cultures

Monnerie,

Romer,

Roth

et al. 2023

Front. Mol. Neurosci.

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Combined antiretroviral therapy (cART) has greatly decreased mortality and morbidity among persons with HIV; however, neurologic impairments remain prevalent, in particular HIV-associated neurocognitive disorders (HANDs). White matter damage persists in cART-treated persons with HIV and may contribute to neurocognitive dysfunction as the lipid-rich myelin membrane of oligodendrocytes is essential for efficient nerve conduction. Because of the importance of lipids to proper myelination, we examined the regulation of lipid synthesis in oligodendrocyte cultures exposed to the integrase strand transfer inhibitor elvitegravir (EVG), which is administered to persons with HIV as part of their initial regimen. We show that protein levels of genes involved in the fatty acid pathway were reduced, which correlated with greatly diminished de novo levels of fatty acid synthesis. In addition, major regulators of cellular lipid metabolism, the sterol regulatory element-binding proteins (SREBP) 1 and 2, were strikingly altered following exposure to EVG. Impaired oligodendrocyte differentiation manifested as a marked reduction in mature oligodendrocytes. Interestingly, most of these deleterious effects could be prevented by adding serum albumin, a clinically approved neuroprotectant. These new findings, together with our previous study, strengthen the possibility that antiretroviral therapy, at least partially through lipid dysregulation, may contribute to the persistence of white matter changes observed in persons with HIV and that some antiretrovirals may be preferable as life-long therapy.

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Section: Methodsmentioning

confidence: 99%

Inhibition of lipid synthesis by the HIV integrase strand transfer inhibitor elvitegravir in primary rat oligodendrocyte cultures

Monnerie,

Romer,

Roth

et al. 2023

Front. Mol. Neurosci.

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“…Various HPLC and HPTLC methods were reported in the literature for the estimation of cobicistat and elvitegravir individually [6][7][8] , simultaneously [9][10] and other antiretroviral drugs [10][11][12][13][14][15][16][17][18][19][20] . The present method is novel and was successfully validated in accordance with ICH guidelines 21 .…”

Section: Fig 2: Chemical Structure Of Elvitegravirmentioning

confidence: 99%

Untitled

2019

IJPSR

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A simple, precise, rapid and accurate reverse phase HPLC method was developed for the simultaneous estimation of cobicistat and elvitegravir in the pharmaceutical dosage form. A column of ODS (250mm 4.6mm; i.d and 5µ particle size) was used along with the mobile phase comprising of 0.02M dipotassium hydrogen orthophosphate buffer (pH adjusted to 3.3) and methanol in the ratio of 80:20 (v/v). The flow rate was maintained at 1.0 ml/min and the effluents monitored at 254 nm. The retention time for cobicistat was found to be 2.58 ± 0.3 min and elvitegravir was 3.71 ± 0.3 min. The detection concentration was linear over 125-750 µg/ml for cobicistat and 12.5-75 µg/ml for elvitegravir. Regression equations of cobicistat and elvitegravir were found to be y = 25883x + 19711 and y = 27696x + 6046 respectively with regression coefficient 0.999. The % RSD for Intra and Inter day precision was < 2%. The accuracy of method was validated by recovery studies and found to be significant within acceptable range 98-102%. The developed method was successfully validated in accordance with ICH guidelines. The present study demonstrates the applicability of chromatographic method to develop a new, sensitive, single RP-HPLC method for the simultaneous quantitative determination of cobicistat and elvitegravir in fixed pharmaceutical dosage form. Hence, this method can be conveniently adopted for routine analysis in quality control laboratories.

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HIV-1 escape in the central nervous system on elvitegravir-based antiretroviral therapy

Guerveno

Raymond

Metsu

et al. 2019

Aids

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HIGHLIGHTS OF PRESCRIBING INFORMATIONThese highlights do not include all the information needed to use GENVOYA safely and effectively. See full prescribing information for GENVOYA. GENVOYA ® (elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide) tablets, for oral use Initial U.S. Approval: 2015 WARNING: LACTIC ACIDOSIS/SEVERE HEPATOMEGALY WITH STEATOSIS and POST TREATMENT ACUTE EXACERBATION OF HEPATITIS B See full prescribing information for complete boxed warning. * Sections or subsections omitted from the full prescribing information are not listed. Gilead SciencesReference ID: 4023346 * Indicates that a drug-drug interaction trial was conducted. a. See Drug Interactions (7), Table 5 for sildenafil when used for erectile dysfunction.

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

Cited by 3 publications

References 17 publications

Inhibition of lipid synthesis by the HIV integrase strand transfer inhibitor elvitegravir in primary rat oligodendrocyte cultures

Inhibition of lipid synthesis by the HIV integrase strand transfer inhibitor elvitegravir in primary rat oligodendrocyte cultures

Untitled

HIV-1 escape in the central nervous system on elvitegravir-based antiretroviral therapy

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