Article

Simultaneous determination of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma by reversed-phase high-performance liquid chromatography.

Clinical Pharmacology Unit, Hospital Clínic, Barcelona, Spain.
Journal of chromatography. B, Biomedical sciences and applications 07/2001; 757(2):325-32. DOI:10.1016/S0378-4347(01)00172-4 pp.325-32
Source: PubMed

ABSTRACT A rapid, simple and sensitive high-performance liquid chromatographic (HPLC) assay has been developed for the simultaneous quantification of the HIV-protease inhibitors indinavir, amprenavir, ritonavir, saquinavir and nelfinavir in human plasma. The method involved the solid-phase extraction of the five drugs and the internal standard (I.S., verapamil) from 400 microl of human plasma. The HPLC analysis used a reversed-phase C18 analytical column and a mobile phase consisting of a gradient with 15 mM phosphate buffer (pH 5.75)-acetonitrile and UV monitoring. The method was linear over the therapeutic concentration range for the five HIV-protease inhibitors. The accuracy of the method ranged from 98.2 to 106.7% and the precision values ranged from 1.4 to 8.1% for intra-day precision and from 3.1 to 6.4% for the inter-day values.

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    Article: Comparison of levels of antiretroviral drugs with efficacy in children with HIV infection.
    Ana Pilar Nso, Beatriz Larru, Jose Ma Bellón, Ma José Mellado, Jose Tomás Ramos, Ma Isabel González, María Luisa Navarro, María Angeles Muñoz-Fernández, María Isabel de José
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    ABSTRACT: To determine the prevalence of low and high antiretroviral (ARV) plasma levels and to analyze correlation between ARV concentrations and the appearance of therapeutic failure and toxicity. The authors present here a study evaluating antiretroviral plasma concentrations in HIV infected children on nonnucleoside reverse transcriptase inhibitors and protease inhibitors based therapy. The authors carried out a multicentre, cross-sectional study, including HIV-infected children from five large Hospitals in Madrid, Spain. Clinical, haematological, biochemical and immuno-virological parameters were assessed. Antiretroviral plasma trough levels were performed using a validated high performance liquid chromatography method. Between April 2006 and April 2008, 129 children were enrolled in the present study, with median treatment duration of 39.2 months. 25.5% of the non-nucleoside reverse transcriptase inhibitors levels were low and 17.6%, high. 27.9% percent of the protease inhibitors levels were low and 12.5%, high. A correlation was found among adequate or high levels of antiretrovirals and normal CD4 percentage and low viral load. Lopinavir/ritonavir plasma levels were correlated with an increase in lipodystrophy. Patients with Tanner stage 1 presented the lowest ARV plasma levels. Full adherence was reported for all the participants by a questionnaire. Many HIV-infected children show ARV plasma levels out of the therapeutic range which demands a child-adjusted approach. However, larger studies are urgently needed in pediatric populations to define optimal reference values.
    The Indian Journal of Pediatrics 04/2010; 77(4):397-402. · 0.52 Impact Factor
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Keywords

five drugs
 
five HIV-protease inhibitors
 
HIV-protease inhibitors indinavir
 
human plasma
 
inter-day values
 
internal standard
 
mobile phase
 
pH 5.75)-acetonitrile
 
rapid
 
reversed-phase C18 analytical column
 
ritonavir
 
sensitive high-performance liquid chromatographic
 
solid-phase extraction
 
therapeutic concentration range
 
UV monitoring