Simultaneous quantification of the new HIV protease inhibitors atazanavir and tipranavir in human plasma by high-performance liquid chromatography coupled with electrospray ionization tandem mass spectrometry

Crommentuyn, Kristel M. L.; Rosing, Hilde; Hillebrand, M. J. X.; Huitema, Alwin D. R.; Beijnen, Jos H.

doi:10.1016/j.jchromb.2004.01.041

Cited by 55 publications

(68 citation statements)

References 6 publications

(14 reference statements)

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“…Most of the fragmentations presented involve the loss of m/z 64 (SO 2 ) from the structure without loss of the distal amine. This extraction of the SO 2 moiety from sulphonamide structures has been observed earlier, although the exact mechanism remains unclear [17][18][19].…”

Section: Discussionsupporting

confidence: 69%

Human metabolism of [14C]indisulam following i.v. infusion in cancer patients

et al. 2005

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Indisulam is a new anticancer drug with a unique mechanism of action, arresting the cell cycle at the G1/S transition. The major excretory pathway of indisulam is via the urine, accounting for 63% of the radioactive dose ([(14)C]indisulam) administered in a human mass balance study. Radiochromatographic profiling of urine samples resulted in the detection of several radioactive peaks. The purpose of the present investigation was to elucidate the chemical structures of these observed indisulam metabolites. We collected fractions after chromatographic separation of the urine samples. These fractions were analysed using tandem mass spectrometry. We propose the chemical structure of 15 indisulam metabolites in urine. The metabolism of indisulam is very complex, consisting of oxidative dechlorination, hydroxylation, hydrolysis, acetylation, sulphation and glucuronidation. The clinical relevance of the observed indisulam metabolites needs further investigation.

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Section: Discussionsupporting

confidence: 69%

Human metabolism of [14C]indisulam following i.v. infusion in cancer patients

et al. 2005

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“…This recovery was significantly higher compared with previously reported values: 77.1 ± 4.0% (Colombo et al, 2005), 69.8-71.2% (Giraud et al, 2006) and 88-91% (Crommentuyn et al, 2004).…”

Section: Validationcontrasting

confidence: 68%

“…A combined bioanalytical assay for atazanavir and tipranavir has already been published using LC-MSMS (Crommentuyn et al, 2004). We therefore expected that bioanalysis would also be possible using LC-UV.…”

Section: Resultsmentioning

confidence: 99%

“…In addition to liquid chromatographic assays with tandem MS detection, UV detection may play a role because of its better availability, lower cost and the high plasma levels of the drug. In addition to one LC-MSMS assay published for tipranavir (Crommentuyn et al, 2004), two assays using UV detection have been reported very recently (Colombo et al, 2006;Giraud et al, 2006). We started to validate an isocratic LC-UV method for tipranavir using the assay we previously developed for the newest peptidic PI, atazanavir (Sparidans et al, 2006) …”

Section: Introductionmentioning

confidence: 99%

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Liquid chromatographic assay for the non-peptidic protease inhibitor tipranavir in plasma

Sparidans

Dost

Crommentuyn

et al. 2006

Biomed. Chromatogr.

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Tipranavir is the most recently introduced protease inhibitor for the suppression of the human immunodeficiency virus (HIV). A selective reversed-phase liquid chromatographic assay, previously developed for atazanavir, has been extended and validated for tipranavir in plasma. Compounds were isolated from a 500 microL plasma sample using liquid-liquid extraction with dichloromethane. After evaporation and reconstitution of the extract the sample was analysed using reversed-phase liquid chromatography and ultra violet detection at 280 nm. In the evaluated concentration range (0.2-50 microg/mL tipranavir), intra-day precisions were

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“…For drug discovery, protein precipitation (PP) is the most common sample preparation procedure; liquid-liquid extraction (LLE) and solid-phase extraction (SPE) have also been reported as preparation techniques for plasma samples (1,3,(11)(12)(13)(14)(15)(16)(17)(18)(19)(20). PP is the simplest approach because it requires no method development, and it removes the majority of the protein from the sample.…”

Section: Sample Preparationmentioning

confidence: 99%