Intracellular measurements of anti-HIV drugs indinavir, amprenavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, efavirenz and nevirapine in peripheral blood mononuclear cells by liquid chromatography coupled to tandem mass spectrometry

Colombo, Sara; Béguin, Alexandre; Telenti, Amalio; Biollaz, J; Buclin, Thierry; Rochat, Bertrand; Décosterd, Laurent A.

doi:10.1016/j.jchromb.2005.02.010

Cited by 110 publications

(99 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The quantification of nelfinavir in plasma, liver tissue, and cells has been performed with the stable isotope labeled internal standard method using an adaptation of the assay by liquid chromatography tandem mass spectrometry developed in our laboratory (72).…”

Section: Methodsmentioning

confidence: 99%

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

Gassart

Bujisic

Zaffalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Inhibitors of the HIV aspartyl protease [HIV protease inhibitors (HIV-PIs)] are the cornerstone of treatment for HIV. Beyond their well-defined antiretroviral activity, these drugs have additional effects that modulate cell viability and homeostasis. However, little is known about the virus-independent pathways engaged by these molecules. Here we show that the HIV-PI Nelfinavir decreases translation rates and promotes a transcriptional program characteristic of the integrated stress response (ISR). Mice treated with Nelfinavir display hallmarks of this stress response in the liver, including α subunit of translation initiation factor 2 (eIF2α) phosphorylation, activating transcription factor-4 (ATF4) induction, and increased expression of known downstream targets. Mechanistically, Nelfinavir-mediated ISR bypassed direct activation of the eIF2α stress kinases and instead relied on the inhibition of the constitutive eIF2α dephosphorylation and down-regulation of the phophatase cofactor CReP (Constitutive Repressor of eIF2α Phosphorylation; also known as PPP1R15B). These findings demonstrate that the modulation of eIF2α-specific phosphatase cofactor activity can be a rheostat of cellular homeostasis that initiates a functional ISR and suggest that the HIV-PIs could be repositioned as therapeutics in human diseases to modulate translation rates and stress responses.

show abstract

Section: Methodsmentioning

confidence: 99%

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

Gassart

Bujisic

Zaffalon

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Several analytical methods have been published for the analysis of EFV in plasma, either alone or in combination with other drugs, using HPLC-UV [14][15][16][17] and LC-MS/MS [18][19][20][21][22][23] techniques. Determination of EFV levels in human hair [7] and reports of determining nevirapine [8,10] and indinavir [24] from saliva have been published, but this study is the first validated LC-MS/MS method for the assay of EFV in saliva to be reported.…”

Section: Discussionmentioning

confidence: 99%

“…The method reported here incorporates positive electrospray ionization compared to the use of negative electrospray ionization reported by most published articles [19,23,25], allowing for the possibility to detect other antiretroviral drugs in a single run.…”

Section: Discussionmentioning

confidence: 99%

Determination of salivary efavirenz by liquid chromatography coupled with tandem mass spectrometry

Theron

Cromarty

Rheeders

et al. 2010

Journal of Chromatography B

View full text Add to dashboard Cite

a b s t r a c tA novel and robust screening method for the determination of the non-nucleoside reverse transcriptase inhibitor, efavirenz (EFV), in human saliva has been developed and validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation of the saliva involved solid-phase extraction (SPE) on C18 cartridges. The analytes were separated by high performance liquid chromatography (Phenomenex Kinetex C18, 150 mm × 3 mm internal diameter, 2.6 m particle size) and detected with tandem mass spectrometry in electrospray positive ionization mode with multiple reaction monitoring. Gradient elution with increasing methanol (MeOH) concentration was used to elute the analytes, at a flow-rate of 0.4 mL/min. The total run time was 8.4 min and the retention times for the internal standard (reserpine) was 5.4 min and for EFV was 6.5 min. The calibration curves showed linearity (r 2 , 0.989-0.992) over the concentration range of 3.125-100 g/L. Mean intra-and inter-assay relative standard deviation, accuracy, mean extraction recovery, limit of detection (LOD) and limit of quantification (LOQ) were 0.46-9.43%, 80-120%, 60% (±7.95), 1.84 and 6.11 g/L respectively. The working range was defined as 6.25-100 g/L. This novel LC-MS/MS assay is suitable for reliable detection of low EFV concentrations in saliva and can be used as a screening tool for monitoring EFV compliance.

show abstract

“…The six calibration standards and three quality controls (QCs) were prepared adding a determined volume of stock solutions, or diluted stock solution, to each blank PBMCs aliquots before storage at -80°C, during no more than three months, in a manner similar to that described in other publications [43][44].…”

Section: Stock Solutions Standards (Std) and Quality Controls (Qc)mentioning

confidence: 99%

HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC)

D’Avolio¹,

Simiele²,

Francia

et al. 2012

Journal of Pharmaceutical and Biomedical Analysis

View full text Add to dashboard Cite

A new method using high performance liquid chromatography coupled with electrospray mass spectrometry is described for the quantification of PBMC concentration of tyrosine kinase inhibitors imatinib, dasatinib and nilotinib. A simple PBMC isolation and extraction procedure were applied on 10-14 mL of blood aliquots. Chromatographic separation of drugs and Internal Standard (quinoxaline) was achieved with a gradient (acetonitrile and water + formic acid 0.05%) on a C18 reverse phase analytical column with 25 min of analytical run, at flow rate of 0.25 mL/min. Mean intra-and inter-day precision for all compounds were 8.76 and 12.20%; mean accuracy was -3.86%; extraction recovery ranged within 79 and 91%. Calibration curves ranged from 50.0 to 0.25 ng. The limit of quantification was set at 0.25 ng for all the analyzed drugs.This novel developed methodology allows a specific, sensitive and reliable simultaneous intracellular determination of the three tyrosine kinase inhibitors imatinib, dasatinib and nilotinib in a single chromatographic run, useful for drugs estimation in PBMC of patients affected by chronic myeloid leukemia.

show abstract

Intracellular measurements of anti-HIV drugs indinavir, amprenavir, saquinavir, ritonavir, nelfinavir, lopinavir, atazanavir, efavirenz and nevirapine in peripheral blood mononuclear cells by liquid chromatography coupled to tandem mass spectrometry

Cited by 110 publications

References 49 publications

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

An inhibitor of HIV-1 protease modulates constitutive eIF2α dephosphorylation to trigger a specific integrated stress response

Determination of salivary efavirenz by liquid chromatography coupled with tandem mass spectrometry

HPLC–MS method for the simultaneous quantification of the antileukemia drugs imatinib, dasatinib and nilotinib in human peripheral blood mononuclear cell (PBMC)

Contact Info

Product

Resources

About