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Determination of abacavir, tenofovir, darunavir, and raltegravir in human plasma and saliva using liquid chromatography coupled with tandem mass spectrometry.
Yamada, Eiko; Takagi, Ritsuo; Sudo, Koji; Kato, Shingo.
Afiliação
  • Yamada E; Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata 951 8510, Japan.
  • Takagi R; Division of Oral and Maxillofacial Surgery, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata 951 8510, Japan.
  • Sudo K; Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 8582, Japan.
  • Kato S; Department of Microbiology and Immunology, Keio University School of Medicine, 35 Shinanomachi, Shinjuku-ku, Tokyo 160 8582, Japan. Electronic address: skato@a3.keio.jp.
J Pharm Biomed Anal ; 114: 390-7, 2015 Oct 10.
Article em En | MEDLINE | ID: mdl-26112927
ABSTRACT
A liquid chromatography-tandem mass spectrometry assay for the determination of abacavir (ABC), tenofovir (TFV), darunavir (DRV), and raltegravir (RAL) in human plasma and saliva was developed and validated to investigate the applicability of saliva as an appropriate specimen for therapeutic drug monitoring. As internal standards, TFV was chosen for ABC, ABC was chosen for TFV, RAL for DRV, and DRV for RAL. Sample preparation involved protein precipitation with acetonitrile, evaporation of solvent using a centrifugal evaporator, and reconstitution by dissolving the residue in mobile phase. Liquid chromatography was performed on a C18 reverse phase column (1.5 × 50 mm, 5 µm) isocratically at a flow rate of 0.2 mL/min using 5mM formic acid-3% (v/v) acetonitrile as the mobile phase for ABC and TFV and 5mM formic acid-35% (v/v) acetonitrile as the mobile phase for DRV and RAL. The run time was 6 min, and the retention time was approximately 2.0 min for TFV, 2.5 min for RAL, and 4-4.5 min for ABC and DRV. Analytes were detected using tandem mass spectrometry in positive electrospray ionization mode. The precursor/product ion transitions (m/z) were 287.3/191.2 for ABC, 288.5/176.2 for TFV, 548.3/392.3 for DRV, and 445.3/109.5 for RAL, and were monitored on a triple-quadrupole mass spectrometer operated in the multiple reaction monitoring mode. The linearity of the assay was assessed in the range 1-10,000 ng/mL for all four drugs. Within-run and between-run mean accuracy, precision, and the extraction recovery for all drugs were -14.5-18.1%, 1.2-13.1%, and 86.0-111.1%, respectively. The proposed assay is sufficiently sensitive and accurate to quantify these drugs in plasma and saliva, and is suitable for investigating the relationship between drug concentrations in plasma and saliva.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saliva / Didesoxinucleosídeos / Darunavir / Tenofovir / Raltegravir Potássico Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: J Pharm Biomed Anal Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Japão

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Saliva / Didesoxinucleosídeos / Darunavir / Tenofovir / Raltegravir Potássico Tipo de estudo: Guideline Limite: Humans Idioma: En Revista: J Pharm Biomed Anal Ano de publicação: 2015 Tipo de documento: Article País de afiliação: Japão