Universal efavirenz determination in transport study, rat placenta perfusion and placenta lysate by HPLC-UV
Language English Country England, Great Britain Media print-electronic
Document type Journal Article
PubMed
28092857
DOI
10.1016/j.jpba.2017.01.012
PII: S0731-7085(16)31066-4
Knihovny.cz E-resources
- Keywords
- Drug transporters, Drug-drug interactions, Efavirenz, Liquid chromatography, Pharmacokinetics, Stability,
- MeSH
- ATP Binding Cassette Transporter, Subfamily G, Member 2 metabolism MeSH
- Acetonitriles chemistry MeSH
- Alkynes MeSH
- Benzoxazines chemistry metabolism MeSH
- Biological Transport physiology MeSH
- Cell Line MeSH
- Madin Darby Canine Kidney Cells MeSH
- Cyclopropanes MeSH
- Rats MeSH
- ATP Binding Cassette Transporter, Subfamily B, Member 1 metabolism MeSH
- Perfusion MeSH
- Placenta chemistry MeSH
- Rats, Wistar MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins metabolism MeSH
- Dogs MeSH
- Reproducibility of Results MeSH
- Drug Stability MeSH
- Pregnancy MeSH
- Chromatography, High Pressure Liquid methods MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Dogs MeSH
- Pregnancy MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Names of Substances
- ATP Binding Cassette Transporter, Subfamily G, Member 2 MeSH
- acetonitrile MeSH Browser
- Acetonitriles MeSH
- Alkynes MeSH
- Benzoxazines MeSH
- Cyclopropanes MeSH
- efavirenz MeSH Browser
- ATP Binding Cassette Transporter, Subfamily B, Member 1 MeSH
- Multidrug Resistance-Associated Protein 2 MeSH
- Multidrug Resistance-Associated Proteins MeSH
Efavirenz is an antiretroviral drug used in the treatment of HIV-positive patients. A simple, fast and sensitive high-performance liquid chromatography (HPLC) method was developed in order to determine efavirenz in three types of samples provided from pharmacokinetic studies. The analysis took 5min and was performed using a C18 analytical column (Discovery HS C18, 150×4.6mm, particle size of 5μm) in isocratic mode with a mobile phase containing acetonitrile and water (65:35, v/v), a flow rate of 1.6mLmin-1, a sample volume of 10μL and UV detection at 245nm. Three different sample matrices (Opti-MEM medium, Krebs perfusion liquid and tissue lysate) and their treatment (dilution, SPE) were considered. The validated method was applied for the analysis of 805 real samples arising from in vitro transcellular transport assays and in vivo organ perfusion experiments in order to evaluate the interaction of efavirenz with ATP-dependent drug efflux transporters. The lack of interaction of efavirenz with ABCB1, ABCG2 and ABCC2 transporters as well as technical aspects of this analysis, including the adhesion of efavirenz to the plastic materials and the stability of the drug during different tissue lysis approaches are discussed.
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