The Experts below are selected from a list of 7989 Experts worldwide ranked by ideXlab platform
B K Matuszewski - One of the best experts on this subject based on the ideXlab platform.
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effect of the sample matrix on the determination of indinavir in human urine by hplc with turbo ion spray tandem mass spectrometric detection
Journal of Pharmaceutical and Biomedical Analysis, 1998Co-Authors: I Fu, Eric Woolf, B K MatuszewskiAbstract:Abstract The HPLC/tandem mass spectrometric (LC/MS/MS) behavior of indinavir, an HIV Protease Inhibitor, in human urine is presented as an example of a case where endogenous matrix components were found to interfere with the ionization of the target analyte. The MS/MS system used for these experiments was equipped with a turbo ion spray LC interface. Results from two sample preparation procedures (direct dilution of urine vs urine extraction) and two chromatographic systems (low vs. high capacity factor ( k ′)) for the analytes were compared. Additionally, the precision of the analysis that was achieved while using a stable isotope labeled internal standard is contrasted with the results obtained using an analog of indinavir as internal standard. The results obtained indicated that during development and validation of LC/MS/MS based assays the potential effect of co-eluting `unseen' endogenous species should be evaluated to ensure that sample preparation and chromatography is adequate to overcome the matrix effect problems.
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determination of l 735 524 an human immunodeficiency virus Protease Inhibitor in human plasma and urine via high performance liquid chromatography with column switching
Journal of Chromatography A, 1995Co-Authors: Eric Woolf, T Au, H Haddix, B K MatuszewskiAbstract:Abstract A method for the determination of an HIV Protease Inhibitor, L-735 524, in human plasma and urine is described. Isolation of the analyte and the internal standard from the matrices was achieved via multiple liquid-liquid extractions with methyl tert. -butyl ether. The analyte lacks significant UV absorption at wavelengths greater than 220 nm, hence a column switching system using a cyano and C 18 column was used to further purify the extracts prior to UV detection at 210 nm. The assay has been found to be linear and has been validated over the concentration range of 5 to 500 ng/ml, when 1-ml aliquots of plasma or urine were extracted. The assay has been utilized to support human pharmacokinetic studies.
Daisy B Whigan - One of the best experts on this subject based on the ideXlab platform.
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liquid chromatography tandem mass spectrometric quantitative determination of the HIV Protease Inhibitor atazanavir bms 232632 in human peripheral blood mononuclear cells pbmc practical approaches to pbmc preparation and pbmc assay design for high th
Journal of Chromatography B, 2003Co-Authors: Mohammed Jemal, Michael Gatz, Daisy B WhiganAbstract:A selective, accurate, and reproducible LC/MS/MS assay was developed and validated for the determination of the HIV Protease Inhibitor atazanavir (BMS-232632) in human peripheral blood mononuclear cells (PBMC) samples. In addition to the details of the validated LC/MS/MS method, a practical procedure is described in great detail for the preparation of large supplies of control (blank) PBMC from units of blood (each unit of blood is about 500 ml) for making the calibration standards and quality control (QC) samples. The PBMC assay design, intended for high-throughput sample analysis, is also described in some detail in regards to the composition and concentration expressions of the calibration standards and QC samples, the lysing procedure of the PBMC samples, and the final analysis/quantitation procedure. The method involved automated solid-phase extraction (SPE) of atazanavir and a stable isotope analog internal standard (I.S.) using 3M Empore C2-SD 96-well plates. A portion of the reconstituted sample residue was injected onto a YMC Basic analytical column which was connected to a triple quad mass spectrometer for analyte determination by positive-ion electrospray in the selected reaction monitoring (SRM) mode. The standard curve, which ranged from 5 to 2500 fmol per one million cells (fmol/10(6) cells), was fitted to a quadratic regression model weighted by 1/concentration. The lower limit of quantitation (LLOQ) was 5 fmol/10(6) cells. The inter- and intra-run coefficients of variation (CV) for the assay were <9% and the accuracy was 94-104%. Atazanavir was stable in PBMC for at least 24h at room temperature and for at least 129 days at -15 degrees C.
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quantitative determination of the HIV Protease Inhibitor atazanavir bms 232632 in human plasma by liquid chromatography tandem mass spectrometry following automated solid phase extraction
Journal of Chromatography B, 2003Co-Authors: Alan Schuster, S Burzawa, Mohammed Jemal, E Loizillon, Philippe Couerbe, Daisy B WhiganAbstract:A selective, accurate, and reproducible LC–MS–MS assay was developed for the determination of the HIV Protease Inhibitor atazanavir (BMS-232632) in human plasma samples. The method involved automated solid-phase extraction of atazanavir and a stable isotope analog internal standard (I.S.) using Oasis HLB 10 mg 96-well SPE plates. A portion of the reconstituted sample residue was injected onto a C18 HDO analytical column which was configured with a triple quad mass spectrometer for analyte determination by positive ion electrospray. The assay was linear from 1.00 to 1000 ng/ml with a lower limit of quantitation of 1.00 ng/ml. The inter- and intra-day coefficients of variation (C.V.) for the assay were <4%, and the accuracy was 99–102%. Atazanavir was stable in human plasma for at least 109 h at room temperature and for at least 1 year at −20 °C.
Richard M W Hoetelmans - One of the best experts on this subject based on the ideXlab platform.
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clinical perspective on antiretroviral drug drug interactions with the non nucleoside reverse transcriptase Inhibitor etravirine
Antiviral Therapy, 2010Co-Authors: Thomas N Kakuda, Monika Schollergyure, Richard M W HoetelmansAbstract:Etravirine is an effective and well-tolerated recently approved non-nucleoside reverse transcriptase Inhibitor (NNRTI) for HIV type-1-infected patients with previous antiretroviral treatment experience. Considering the importance of combining antiretrovirals for their optimal use in treating HIV, a number of drug-drug interactions with etravirine and other antiretrovirals have been evaluated. Etravirine is a weak inducer of cytochrome P450 (CYP)3A and a weak Inhibitor of CYP2C9/CYP2C19 and P-glycoprotein, and although etravirine is metabolized by the CYP enzyme system, the extent of clinically relevant interactions with other antiretrovirals is limited. Etravirine can be combined with all currently available nucleoside/nucleotide reverse transcriptase Inhibitors without dose adjustments, but not with other NNRTIs. Available data indicate that etravirine can be coadministered with most of the currently available ritonavir-boosted HIV Protease Inhibitors. Coadministration with tipranavir/ritonavir or unboosted HIV Protease Inhibitors is not recommended because of clinically relevant changes in exposure to etravirine or the coadministered HIV Protease Inhibitor, respectively. Etravirine can be coadministered with the integrase Inhibitors elvitegravir/ritonavir or raltegravir, and with the fusion Inhibitor enfuvirtide, without dose adjustments. Dose adjustment of the C-C chemokine receptor type-5 antagonist maraviroc is required, with the type of adjustment depending on whether a boosted HIV Protease Inhibitor is included in the regimen. In conclusion, etravirine can be combined with most antiretrovirals, with no clinically meaningful effect on drug exposure or safety/tolerability profiles.
Laurent A Decosterd - One of the best experts on this subject based on the ideXlab platform.
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determination of the novel non peptidic HIV Protease Inhibitor tipranavir by hplc uv after solid phase extraction
Journal of Chromatography B, 2006Co-Authors: Sara Colombo, A Beguin, C Marzolini, A Telenti, J Biollaz, Laurent A DecosterdAbstract:Abstract An HPLC method previously described for the assay of amprenavir (APV), ritonavir (RTV), indinavir (IDV), saquinavir (SQV), nelfinavir (NFV), lopinavir (LPV), atazanavir (ATV), nevirapine (NVP) and efavirenz (EFV) can be also conveniently applied, with minor gradient program adjustment, for the determination of the novel non-peptidic HIV Protease Inhibitor tipranavir (TPV) in human plasma, by off-line solid-phase extraction (SPE) followed by HPLC coupled with UV–diode array detection (DAD). After viral inactivation by heat, the plasma is diluted with phosphate buffer (pH 7), and subjected to a SPE on a C18 cartridge. Matrix components are eliminated with a solution of 0.1% H 3 PO 4 solution neutralised to pH 7, and TPV is eluted with MeOH. The resulting eluate is evaporated and reconstituted in 100 μl MeOH/H 2 O 50/50. A 40 μl volume is injected onto a Nucleosil C18 AB column and TPV is analysed by UV detection at 201 nm using a gradient elution program constituted of MeCN and phosphate buffer adjusted to pH 5.12 and containing 0.02% sodium heptanesulfonate. The calibration curves are linear up to 75 μg/ml, with a lower limit of quantification of 0.125 μg/ml. The mean absolute recovery of TPV is 77.1 ± 4.0%. The method is precise with mean inter-day coefficient of variations (CVs) within 2.2–3.4%, and accurate (range of inter-day deviations from 0.7 to 1.2%). The method has been validated and is currently applied to the monitoring of TPV plasma levels in HIV patients.
Eric Woolf - One of the best experts on this subject based on the ideXlab platform.
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effect of the sample matrix on the determination of indinavir in human urine by hplc with turbo ion spray tandem mass spectrometric detection
Journal of Pharmaceutical and Biomedical Analysis, 1998Co-Authors: I Fu, Eric Woolf, B K MatuszewskiAbstract:Abstract The HPLC/tandem mass spectrometric (LC/MS/MS) behavior of indinavir, an HIV Protease Inhibitor, in human urine is presented as an example of a case where endogenous matrix components were found to interfere with the ionization of the target analyte. The MS/MS system used for these experiments was equipped with a turbo ion spray LC interface. Results from two sample preparation procedures (direct dilution of urine vs urine extraction) and two chromatographic systems (low vs. high capacity factor ( k ′)) for the analytes were compared. Additionally, the precision of the analysis that was achieved while using a stable isotope labeled internal standard is contrasted with the results obtained using an analog of indinavir as internal standard. The results obtained indicated that during development and validation of LC/MS/MS based assays the potential effect of co-eluting `unseen' endogenous species should be evaluated to ensure that sample preparation and chromatography is adequate to overcome the matrix effect problems.
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determination of l 735 524 an human immunodeficiency virus Protease Inhibitor in human plasma and urine via high performance liquid chromatography with column switching
Journal of Chromatography A, 1995Co-Authors: Eric Woolf, T Au, H Haddix, B K MatuszewskiAbstract:Abstract A method for the determination of an HIV Protease Inhibitor, L-735 524, in human plasma and urine is described. Isolation of the analyte and the internal standard from the matrices was achieved via multiple liquid-liquid extractions with methyl tert. -butyl ether. The analyte lacks significant UV absorption at wavelengths greater than 220 nm, hence a column switching system using a cyano and C 18 column was used to further purify the extracts prior to UV detection at 210 nm. The assay has been found to be linear and has been validated over the concentration range of 5 to 500 ng/ml, when 1-ml aliquots of plasma or urine were extracted. The assay has been utilized to support human pharmacokinetic studies.