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).

Institute of Organic Chemistry and Biochemistry Academy of Sciences of the Czech Republic Prague Czech Republic

References provided by Crossref.org

An overview of chiral separations of pharmaceutically active substances by HPLC (2018-2020)

9-[2-(R)-(Phosphonomethoxy)propyl]-2,6-diaminopurine (R)-PMPDAP and its prodrugs: optimized preparation, including identification of by-products formed, and antiviral evaluation in vitro