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Titolo:
Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir, nelfinavir and the non-nucleoside reverse transcriptase inhibitor efavirenz by high-performance liquid chromatography after solid-phase extraction
Autore:
Marzolini, C; Telenti, A; Buclin, T; Biollaz, J; Decosterd, LA;
Indirizzi:
CHU Vaudois, Dept Med, Div Clin Pharmacol, CH-1011 Lausanne, Switzerland CHU Vaudois Lausanne Switzerland CH-1011 , CH-1011 Lausanne, Switzerland CHU Vaudois, Duv Malad Infect, Lausanne, Switzerland CHU Vaudois Lausanne Switzerland uv Malad Infect, Lausanne, Switzerland
Titolo Testata:
JOURNAL OF CHROMATOGRAPHY B
fascicolo: 1, volume: 740, anno: 2000,
pagine: 43 - 58
SICI:
1387-2273(20000331)740:1<43:SDOTHP>2.0.ZU;2-R
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN-IMMUNODEFICIENCY-VIRUS; MASS-SPECTROMETRIC DETECTION; HUMAN PLASMA; ULTRAVIOLET DETECTION; CEREBROSPINAL-FLUID; LYMPHOTROPIC VIRUS; SALIVA; INACTIVATION; VALIDATION; URINE;
Keywords:
protease inhibitors; indinavir; amprenavir; saquinavir; ritonavir; nelfinavir; efavirenz;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
34
Recensione:
Indirizzi per estratti:
Indirizzo: Decosterd, LA CHU Vaudois, Dept Med, Div Clin Pharmacol, CH-1011 Lausanne,Switzerland CHU Vaudois Lausanne Switzerland CH-1011 anne, Switzerland
Citazione:
C. Marzolini et al., "Simultaneous determination of the HIV protease inhibitors indinavir, amprenavir, saquinavir, ritonavir, nelfinavir and the non-nucleoside reverse transcriptase inhibitor efavirenz by high-performance liquid chromatography after solid-phase extraction", J CHROMAT B, 740(1), 2000, pp. 43-58

Abstract

As part of an on-going study on the suitability of a formal therapeutic drug monitoring (TDM) of antiviral drugs for improving the management of HIV infection, a high-performance liquid chromatography method has been developed to quantify simultaneously in plasma five HIV protease inhibitors (PIs) (i.e., indinavir, amprenavir, saquinavir, ritonavir, nelfinavir) and the novel non-nucleoside reverse transcriptase inhibitor efavirenz. After viral inactivation by heat (60 degrees C for 60 min), plasma (600 mu l), with clozapine added as internal standard, is diluted 1:1 with phosphate buffer, pH 7 and subjected to a solid-phase extraction on a C-18 cartridge. Matrix components are eliminated with 2x500 mu l of a solution of 0.1% H3PO4 neutralised with NaOH to pH 7. PIs and efavirenz are eluted with 3X500 mu l MeOH. The resulting eluate is evaporated under nitrogen at room temperature and isreconstituted in 100 mu l 50% MeOH. A 40-mu l volume is subjected to HPLC analysis onto a Nucleosil 100, 5 mu m C-18 AB column, using a gradient elution of MeCN and phosphate buffer adjusted to pH 5.15 and containing 0.02% sodium heptanesulfonate: 15:85 at 0 min-->30:70 at 2 min-->32:68 at 8 min-->42:58 at 18 min-->46:54 at 34 min, followed by column cleaning with MeCN-buffer, pH 5.15 (90.10), onto which 0.3% AcOH is added. Clozapine, indinavir,amprenavir, saquinavir, ritonavir, efavirenz and nelfinavir are detected by UV at 201 nm at a retention time of 8.2,, 13.0, 16.3, 21.5, 26.5, 28.7 and 31.9 min, respectively. The total run time for a single analysis is 47 min, including the washing-out and reequilibration steps. The calibration curves are linear over the range 100-10 000 ng/ml. The absolute recovery of PIs/efavirenz is always higher than 88%. The method is precise with mean inter-day relative standard deviations within 2.5-9.8% and accurate (range of inter-day deviations -4.6 to +4.3%). The in vitro stability of plasma spikedwith PIs/efavirenz at 750, 3000 and 9000 ng/ml has been studied at room temperature, -20 degrees C and +60 degrees C. The method has been validated and is currently applied to the monitoring of PIs and efavirenz in HIV patients. This HPLC assay may help clinicians confronted to questionable compliance, side effects or treatment failure in elucidating whether patients are exposed to adequate circulating drug levels. The availability of such an assay represents an essential step in elucidating the utility of a formal TDMfor the optimal follow-up of HN patients. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/01/20 alle ore 17:20:52