Detection and quantitation of PS20, a phosphorothioate oligodeoxynucleotides in monkey plasma.
OBJECTIVE
To establish the method for quantitation of the phosphorothioate oligodeoxynucleotides (S-ODNs) in plasma.


METHODS
Two solid-phase extraction columns combined with a strong anion-exchange column were utilized to remove proteins and lipids in plasma, and the salts were removed by a reverse-phase column followed by dialysis with a 2500 Da-cutoff membrane. The concentration of the tested S-ODNs, PS20, and its metabolites extracted from the plasma were determined by the method of non-gel sieving capillary electrophoresis (NGCE) with diode array detection in the presence of internal standard (IS).


RESULTS
The method was with good base number specificity. Relative standard deviation % of both intra and inter assay were all less than 10 %, and the total mean recovery was about 91 %. The methodology was successfully used to determine the PK behavior of an anti-tumor antisense S-ODNs in monkeys and identify the metabolites with single base difference.


CONCLUSIONS
The combined method of solid-phase extraction and NGCE could be used to study the pharmacokinetics of S-ODNs, and the main parameters of the methodology met the requirement of PK study.
Shan
Ming-Mei
MM
Department of Pharmacology and Toxicology, the Institute of Radiation Medicine, Academy of Military Medical Sciences, Beijing 100850, China.
Song
Hai-Feng
HF
Liu
Xiu-Wen
XW
Tang
Zhong-Ming
ZM
D000818:Animals; D001483:Base Sequence; D019075:Electrophoresis, Capillary; D008253:Macaca mulatta; D009838:Oligodeoxyribonucleotides / Q000097:blood* / Q000235:genetics; D009943:Organophosphorus Compounds / Q000097:blood; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D013873:Thionucleotides / Q000097:blood* / Q000235:genetics
D009838:Oligodeoxyribonucleotides; D009943:Organophosphorus Compounds; D011506:Proteins; D013873:Thionucleotides