Chiral analysis of anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine (tenofovir), and related antiviral acyclic nucleoside phosphonates by CE using beta-CD as chiral selector.
A new CZE method has been developed for chiral analysis of an important anti-acquired immunodeficiency syndrome drug, 9-(R)-[2-(phosphonomethoxy)propyl]adenine ((R)-PMPA, tenofovir), and six related antiviral acyclic nucleoside phosphonates using beta-CD as a chiral selector. The influence of the composition, concentration and pH of the BGE and the type and concentration of chiral selector on enantiomer resolution was investigated. Complete separations of (R,S)-enantiomers of PMPA with very good resolution (R(s)=1.50-3.64) were achieved within a short time (4-15 min) in 20-50 mM sodium borate or sodium tetraborate BGEs, pH 10.0, at 20 mg/mL concentration of beta-CD. (R,S)-enantiomers of five similar PMPA analogs containing purine bases (adenine, diaminopurine or guanine) and hydroxyl or fluor substituents at C3 carbon atom of propyl chain were baseline separated within 10-17 min in 35 mM sodium tetraborate BGE, pH 10.0, at 20 mg/mL beta-CD concentration. Another important antiviral used by acquired immunodeficiency syndrome patients, derived from pyrimidine base cytosine, 1-(S)-[3-hydroxy-2-(phosphonomethoxy)propyl]cytosine (cidofovir), and the (R)-enantiomer of this drug were successfully separated in 50 mM sodium tetraborate BGE, pH 10.5, at 20 mg/mL beta-CD concentration within 45 min. Using the UV-absorption detection at 206 nm, the concentration detection limits of the analyzed acyclic nucleoside phosphonates were determined in the submicromolar to micromolar range (0.15-2.51 microg/mL level).
Solínová
Veronika
V
Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague, Czech Republic.
Kasicka
Václav
V
Sázelová
Petra
P
Holý
Antonín
A
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry; D019380:Anti-HIV Agents / Q000737:chemistry*; D000077404:Cidofovir; D003596:Cytosine / Q000031:analogs & derivatives* / Q000737:chemistry; D004573:Electrolytes; D019075:Electrophoresis, Capillary / Q000379:methods*; D006863:Hydrogen-Ion Concentration; D016014:Linear Models; D063065:Organophosphonates / Q000737:chemistry*; D011687:Purines / Q000737:chemistry; D011743:Pyrimidines / Q000737:chemistry; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D013237:Stereoisomerism; D000068698:Tenofovir; D047392:beta-Cyclodextrins / Q000737:chemistry*
D019380:Anti-HIV Agents; D004573:Electrolytes; D063065:Organophosphonates; D011687:Purines; D011743:Pyrimidines; D047392:beta-Cyclodextrins; D003596:Cytosine; D000068698:Tenofovir; D000225:Adenine; D000077404:Cidofovir