Document Detail


An HPLC-PDA method for the simultaneous quantification of the HIV integrase inhibitor raltegravir, the new nonnucleoside reverse transcriptase inhibitor etravirine, and 11 other antiretroviral agents in the plasma of HIV-infected patients.
MedLine Citation:
PMID:  18824956     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A new method using high-performance liquid chromatography coupled with photo diode array detection was developed and validated for the quantification of plasma concentrations of the human immunodeficiency syndrome integrase inhibitor raltegravir (RGV), the new nonnucleoside reverse transcriptase inhibitor etravirine (ETV), and 11 other antiretroviral agents: ritonavir, atazanavir, lopinavir, nevirapine, efavirenz, saquinavir, indinavir, nelfinavir, and its metabolite M-8, amprenavir, and darunavir. A simple solid phase extraction procedure was applied to 500 microL aliquots of plasma, and chromatographic separation of the drugs and internal standard (quinoxaline) was achieved with a gradient (acetonitrile and phosphate buffer) on an C-18 reverse-phase analytical column with a 28-minute analytical run time. Calibration curves were optimized according to expected ranges of drug concentrations in patients, and the coefficient of determination (r) was higher than 0.998 for all analytes. Mean intraday and interday precisions (percent relative SD) for all compounds were 3.67% and 6.39%, respectively, and mean accuracy (percent deviation from nominal concentration) was -1.17%. Extraction recovery ranged within 75% and 83% for all drugs analyzed. The solid phase extraction and high-performance liquid chromatography coupled with photo diode array method described allow a specific, sensitive, and reliable simultaneous determination of RGV, ETV, and 11 antiretroviral agents in plasma by a single assay. Good extraction efficiency and low limit of quantification make this a suitable method for use in clinical trials and for therapeutic drug monitoring of RGV, protease inhibitors, and nonnucleoside reverse transcriptase inhibitors, including ETV.
Authors:
Antonio D'Avolio; Lorena Baietto; Marco Siccardi; Mauro Sciandra; Marco Simiele; Valentina Oddone; Stefano Bonora; Giovanni Di Perri
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Therapeutic drug monitoring     Volume:  30     ISSN:  1536-3694     ISO Abbreviation:  Ther Drug Monit     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-12-05     Completed Date:  2009-03-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7909660     Medline TA:  Ther Drug Monit     Country:  United States    
Other Details:
Languages:  eng     Pagination:  662-9     Citation Subset:  IM    
Affiliation:
Department of Infectious Diseases, University of Torino, Amedeo di Savoia Hospital, Turin, Italy. antonio.davolio@unito.it
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MeSH Terms
Descriptor/Qualifier:
Anti-Retroviral Agents / blood*
Chromatography, High Pressure Liquid / methods*
Drug Therapy, Combination
HIV Infections / blood*,  drug therapy*
Humans
Pyridazines / blood*
Pyrrolidinones / blood*
Sensitivity and Specificity
Chemical
Reg. No./Substance:
0/Anti-Retroviral Agents; 0/MK 0518; 0/Pyridazines; 0/Pyrrolidinones; 0/etravirine

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