Simultaneous determination of ritonavir and saquinavir, two human immunodeficiency virus protease inhibitors, in human serum by high-performance liquid chromatography

Frappier, Soriana; Breilh, Dominique; Diarte, E; Ba, Burrows; Ducint, Dominique; Pellegrin, J.L.; Saux, Marie-Claude

doi:10.1016/s0378-4347(98)00220-5

Cited by 38 publications

(13 citation statements)

References 10 publications

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“…Plasma samples were purified by solid-phase extraction using a literature method with modification (Frappier et al, 1998). Briefly, 0.25 ml of plasma samples were mixed with 20 l of internal standard (2 g/ml quinidine) and 0.5 ml of 0.18 M ammonium acetate (pH 6.8) before extraction.…”

Section: Methodsmentioning

confidence: 99%

Differential Roles of P-Glycoprotein, Multidrug Resistance-Associated Protein 2, and CYP3A on Saquinavir Oral Absorption in Sprague-Dawley Rats

Usansky¹,

Hu²,

Sinko³

2008

Drug Metab Dispos

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ABSTRACT:The objective of this investigation was to differentiate the roles of P-glycoprotein (Pgp), multidrug resistance-associated protein 2 (Mrp2), and CYP3A on saquinavir ( -(((3-(2-(7-chloro-2-quinolinyl)-(E)-ethenyl)phenyl) ((3-(dimethylamino-3-oxopropyl)thio)methyl)-thio) propanoic acid (MK571)], and/or CYP3A (midazolam). Plasma concentrations of SQV and related metabolites were analyzed by liquid chromatography-tandem mass spectrometry. When given alone, SQV absorption was extremely low both in situ (F a ‫؍‬ 0.07%) and in vivo [C max ‫؍‬ 0.068 g/ml; area under the curve (AUC) ‫؍‬ 6.8 g ⅐ min/ml]. Coadministration of GF120918 boosted SQV absorption by more than 20-fold with decreased variation in AUCs (percent coefficient of variation ‫؍‬ 30% versus 100%). In contrast, coadministration of MK571 or midazolam increased SQV absorption only 2-to 3-fold without improving the variation in AUCs. SQV oral absorption was not further improved when it was given with GF120918 and midazolam or with GF120918 and MK571. The current results provide, for the first time, direct and explicit evidence that the low oral absorption of SQV is controlled by a secretory transporter, Pgp, and not by limited passive diffusion owing to its poor physicochemical properties. Pgp-mediated transport is also responsible for the highly variable oral bioavailability of SQV. In contrast, intestinal Mrp2 and intestinal CYP3A appear to play minor roles in SQV oral bioavailability. Given the differential and complex roles of Pgp and CYP3A in SQV oral absorption, the optimization of AIDS boosting regimens requires careful consideration to avoid therapylimiting drug-drug transporter and enzyme interactions.

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Section: Methodsmentioning

confidence: 99%

Differential Roles of P-Glycoprotein, Multidrug Resistance-Associated Protein 2, and CYP3A on Saquinavir Oral Absorption in Sprague-Dawley Rats

Usansky¹,

Hu²,

Sinko³

2008

Drug Metab Dispos

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“…SQ concentrations in the samples were measured by an HPLC method as previously described (Frappier et al 1998) with a slight modification. The mobile phase consisted of a mixture of acetonitrile: 5 mM potassium phosphate dibasic buffer (55: 45, v/v) adjusted to pH 8 with phosphoric acid and the flow rate was 1 ml/min.…”

Section: Drug Analysismentioning

confidence: 99%

Preparation and performance evaluation of saquinavir laden cationic submicron emulsions

et al. 2009

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“…Bioanalytical procedures are available wherein there is an opportunity to analyze several important drugs within the same therapeutic class (Frappier et al, 1998) or across several therapeutic classes for the purpose of therapeutic monitoring (Frahnert et al, 2003).…”

Section: Bioanalytical Procedures For Determination Of Multiple Drugsmentioning

confidence: 99%

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations

Srinivas

2006

Biomed. Chromatogr.

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The development of sound bioanalytical method(s) is of paramount importance during the process of drug discovery and development culminating in a marketing approval. Although the bioanalytical procedure(s) originally developed during the discovery stage may not necessarily be fit to support the drug development scenario, they may be suitably modified and validated, as deemed necessary. Several reviews have appeared over the years describing analytical approaches including various techniques, detection systems, automation tools that are available for an effective separation, enhanced selectivity and sensitivity for quantitation of many analytes. The intention of this review is to cover various key areas where analytical method development becomes necessary during different stages of drug discovery research and development process. The key areas covered in this article with relevant case studies include: (a) simultaneous assay for parent compound and metabolites that are purported to display pharmacological activity; (b) bioanalytical procedures for determination of multiple drugs in combating a disease; (c) analytical measurement of chirality aspects in the pharmacokinetics, metabolism and biotransformation investigations; (d) drug monitoring for therapeutic benefits and/or occupational hazard; (e) analysis of drugs from complex and/or less frequently used matrices; (f) analytical determination during in vitro experiments (metabolism and permeability related) and in situ intestinal perfusion experiments; (g) determination of a major metabolite as a surrogate for the parent molecule; (h) analytical approaches for universal determination of CYP450 probe substrates and metabolites; (i) analytical applicability to prodrug evaluations-simultaneous determination of prodrug, parent and metabolites; (j) quantitative determination of parent compound and/or phase II metabolite(s) via direct or indirect approaches; (k) applicability in analysis of multiple compounds in select disease areas and/or in clinically important drug-drug interaction studies. A tabular representation of select examples of analysis is provided covering areas of separation conditions, validation aspects and applicable conclusion. A limited discussion is provided on relevant aspects of the need for developing bioanalytical procedures for speedy drug discovery and development. Additionally, some key elements such as internal standard selection, likely issues of mass detection, matrix effect, chiral aspects etc. are provided for consideration during method development.

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Simultaneous determination of ritonavir and saquinavir, two human immunodeficiency virus protease inhibitors, in human serum by high-performance liquid chromatography

Cited by 38 publications

References 10 publications

Differential Roles of P-Glycoprotein, Multidrug Resistance-Associated Protein 2, and CYP3A on Saquinavir Oral Absorption in Sprague-Dawley Rats

Differential Roles of P-Glycoprotein, Multidrug Resistance-Associated Protein 2, and CYP3A on Saquinavir Oral Absorption in Sprague-Dawley Rats

Preparation and performance evaluation of saquinavir laden cationic submicron emulsions

Applicability of bioanalysis of multiple analytes in drug discovery and development: review of select case studies including assay development considerations

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