Determination of new anti-HIV agents, the KR-V series, in rat plasma using microbore high-performance liquid chromatography

HPLC를 이용한 랫드혈장내 새로운 항HIV제 KR-V series의 분석법

  • Lee, Young-mi (Department of Pharmacokinetics & Toxicokinetics, Korea Research Institute of Chemical Technology) ;
  • Park, Myung-jin (Department of Pharmacokinetics & Toxicokinetics, Korea Research Institute of Chemical Technology) ;
  • Kim, Jin-suk (College of Veterinary Medicine, Konkuk University, Korea) ;
  • Shin, Ho-chul (Department of Pharmacokinetics & Toxicokinetics, Korea Research Institute of Chemical Technology)
  • 이영미 (한국화학연구소 약물독성동태연구실) ;
  • 박명진 (한국화학연구소 약물독성동태연구실) ;
  • 김진석 (건국대학교 수의과대학) ;
  • 신호철 (한국화학연구소 약물독성동태연구실)
  • Accepted : 2000.09.06
  • Published : 2000.12.20

Abstract

We have developed a rapid, simple and precise high-performance liquid chromatographic (HPLC) method using an UV detection system for the determination of new anti-HIV candidates, nineteen KR-V compounds, in rat plasma. We used a analytical columnn of $C_{18}$ ($5{\mu}m$, $250{\times}2.0mm$ I.D.) and a mobile phase of water and ACN mixture (40/60, v/v). Under these conditions, all the KR-V compounds were readily separated from plasma with retention times of 4-12 min. The limits of quantitation for the 19 KR-V compounds were 15-30 ng/ml. The recoveries from the plasma were higher than 85% (C.V.<10%) with exception of KR-V 2, 7 and 15. The compounds KR-V 2, 7 and 15, containing ester moieties, were found to be unstable in plasma. This result suggests that esters, like KR -V 2, 7 and 15, should be excluded from future structure design studies of anti-HIV KR-V agents. In conclusion, the current HPLC method is a valuable analytical tool for investigating the pharmacokinetics of the KR-V series in rats.