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LC-MS/MS를 이용한 혈장 중 레르카니디핀의 분석

Determination of lercanidipine in human plasma by LC-MS/MS

  • 장문선 (바이오코아(주) 신약개발지원사업부) ;
  • 나숙희 (바이오코아(주) 신약개발지원사업부) ;
  • 장규영 (바이오코아(주) 신약개발지원사업부) ;
  • 강승우 (바이오코아(주) 신약개발지원사업부) ;
  • 한상범 (중앙대학교 약학대학) ;
  • 이경률 (바이오코아(주) 신약개발지원사업부) ;
  • 이희주 (바이오코아(주) 신약개발지원사업부)
  • Jang, Moon-Sun (Drug Development Supporting Service Division, BioCore Co., Ltd.) ;
  • La, Sookie (Drug Development Supporting Service Division, BioCore Co., Ltd.) ;
  • Chang, Kyu Young (Drug Development Supporting Service Division, BioCore Co., Ltd.) ;
  • Kang, Seung Woo (Drug Development Supporting Service Division, BioCore Co., Ltd.) ;
  • Han, Sang Beom (College of Pharmacy, ChungAng University) ;
  • Lee, Kyung Ryul (Drug Development Supporting Service Division, BioCore Co., Ltd.) ;
  • Lee, Hee Joo (Drug Development Supporting Service Division, BioCore Co., Ltd.)
  • 투고 : 2007.10.08
  • 심사 : 2008.01.15
  • 발행 : 2008.02.25

초록

LC-MS/MS를 이용하여 신속하고 정확한 혈장 중 레르카니디핀의 분석법을 개발하고 이 분석법에 대한 검증을 수행하였다. 혈장에 내부표준물질로 사용한 암로디핀을 첨가한 후 아세토니트릴로 단백질을 침전시키고, 그 상층액을 취하여 건조시킨 후 50 % 아세토니트릴로 재용해하여 LC-MS/MS로 분석하였다. MS/MS의 MRM (multiple reaction monitoring) 방법을 이용하여 혈장 중 레르카니디핀을 어떠한 분석의 방해물 없이 선택적으로 검출할 수 있었다. 레르카니디핀의 표준 검량선은 0.05-20 ng/mL의 농도 범위에서 우수한 직선성(r = 0.9994)을 보였으며, 일내, 일간 재현성은 변동계수 11.7% 이하, 정확성은 94.4-114.8%로 레르카니디핀의 약물동력학적 연구에 적용되기에 충분한 감도와 특이성, 직선성, 정밀성 및 정확성을 가지고 있음을 확인하였다.

Liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed and validated for the quantitative determination of lercanidipine in human plasma. After addition of internal standard (amlodipine), plasma was precipitated with acetonitrile and the supernatant was evaporated. The residues were dissolved in 50 % acetonitrile and analyzed by LC-MS/MS. Using MS/MS with multiple reaction monitoring(MRM) mode, lercanindipine were selectively detected without severe interference from human plasma. The standard calibration curve for lercanidipine was linear (r = 0.9994) over the concentration range 0.05-20.0 ng/mL in human plasma. The intra- and inter-day precision over the concentration range of lercanidipine was lower than 11.7 % (correlation of variance, CV), and accuracy was between 94.4-114.8 %. This method has been successfully applied to the pharmacokinetic study of lercanidipine in human plasma.

키워드

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