The development and application of a novel LC-MS/MS method for the measurement of Dolutegravir, Elvitegravir and Cobicistat in human plasma.
Dolutegravir and Elvitegravir belongs to a class of integrase inhibitors which has recently been approved by the FDA for the treatment of HIV-infection. Elvitegravir and its co-administered booster drug, Cobicistat, has shown the potential to be a candidate for a one pill once a day regimen and is currently a component of many clinical trials. A sensitive LC-MS/MS method has been developed and validated for the simultaneous determination of these three drugs in human plasma. A liquid- liquid extraction was used as a sample preparation technique using 100μL of plasma. The method was validated from 10 to 4000ng/mL for Dolutegravir, Elvitegravir and Cobicistat. Chromatography was performed on XBridge C18 2.1mm×50mm column, using an 80:20 methanol/water mobile phase containing 0.1% formic acid on a gradient program. This method was successfully applied for ongoing clinical trials.
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK. Electronic address: sujan@liv.ac.uk.
Sujan Dilly
SD
Penchala
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Sandra
S
Fawcett
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Laura
L
Else
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Deirdre
D
Egan
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Alieu
A
Amara
St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
Emilie
E
Elliot
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Elizabeth
E
Challenger
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
David
D
Back
St. Stephen's Centre, Chelsea and Westminster Hospital, London, UK.
Marta
M
Boffito
Department of Molecular & Clinical Pharmacology, University of Liverpool, Liverpool, UK.
Saye
S
Khoo
D019380:Anti-HIV Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000069547:Cobicistat / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy; D019428:HIV Integrase Inhibitors / Q000097:blood; D006575:Heterocyclic Compounds, 3-Ring / Q000097:blood*; D006801:Humans; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones / Q000097:blood*; D053719:Tandem Mass Spectrometry / Q000379:methods*; D000099226:Dolutegravir
D019380:Anti-HIV Agents; D000069547:Cobicistat; D019428:HIV Integrase Inhibitors; D006575:Heterocyclic Compounds, 3-Ring; D010078:Oxazines; D010879:Piperazines; D011728:Pyridones; D015363:Quinolones; D000099226:Dolutegravir; C509700:elvitegravir
Cobicistat; Dolutegravir; Elvitegravir; LC–MS/MS; Method validation