Analysis of various nucleosides in plasma using solid phase extraction and high-performance liquid chromatography with UV detection.
J Pharm Biomed Anal
; 19(6): 955-65, 1999 May.
Article
em En
| MEDLINE
| ID: mdl-10698562
ABSTRACT
The National Cancer Institute (NCI) has screened many nucleosides for antiviral activity to the HIV-1 virus. Drugs demonstrating antiviral activity are tested in animal models to evaluate their toxicity and pharmacokinetic characteristics. These drugs are subsequently evaluated for efficacy in human clinical trials. Sensitive analytical methodology is needed to quantify nucleosides in plasma and other biological matrices in support of these studies. Battelle has modified and validated a reversed phase high-performance liquid chromatography (HPLC) method for several of these nucleosides that could be easily adapted for similar compounds. Methods have been validated for 6-chloro-2',3'-dideoxyguanosine (6ClddG), 6-chloro-2',3'-dideoxyinosine (6ClddI) and their primary metabolites 2',3'-dideoxyguanosine (ddG) and 2',3'-dideoxyinosine (ddI) in both rat and dog plasma containing EDTA. The method has also been validated for 2'-fluoro-2',3'-dideoxyara-adenosine (betaFlddA) and its primary metabolite 2'-beta-fluorodideoxyinosine (betaFddI) in rat plasma containing heparin. Calibration plasma standards were prepared over ranges of 0.1-10 microg ml(-1) for betaFlddA and betaFddI, 0.1-50 microg ml(-1) for 6ClddG and ddG, and 0.25-50 microg ml(-1) for 6ClddI and ddI in plasma containing 4 microg ml(-1) pentostatin. The addition of pentostatin to the plasma samples inhibits in-vitro deamination of the drug after collection. Quality control (QC) standards were prepared containing the appropriate anticoagulant and 4 microg ml(-1) pentostatin at concentrations within each of the bracketed calibration ranges in plasma. These methods have been successfully applied to plasma samples generated during various animal studies.
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Base de dados:
MEDLINE
Assunto principal:
Cromatografia Líquida de Alta Pressão
/
Nucleosídeos
Tipo de estudo:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
J Pharm Biomed Anal
Ano de publicação:
1999
Tipo de documento:
Article
País de afiliação:
Estados Unidos