Journal of Pharmaceutical Investigation

  • 제40권2호
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  • Pages.101-107
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  • 2010
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  • 2093-5552(pISSN)
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  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
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흰쥐에서 항염증제 후보물질 KAL-1120의 HPLC 분석 및 약물동태

HPLC Analysis and Pharmacokinetics of KAL-1120, a Novel Anti-inflammation Agent, in Rats

  • 신대환 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단) ;
  • 이중열 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단) ;
  • 박승혁 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단) ;
  • 이경복 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단) ;
  • 한건 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단) ;
  • 정연복 (충북대학교 약학대학, 충북BIT연구중심대학육성사업단)
  • Shin, Dae-Hwan (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Lee, Jung-Yeol (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Park, Seong-Hyeok (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Lee, Gyeong-Bok (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Han, Kun (CBITRC, College of Pharmacy, Chungbuk National University) ;
  • Chung, Youn-Bok (CBITRC, College of Pharmacy, Chungbuk National University)
  • 투고 : 2010.03.29
  • 심사 : 2010.04.15
  • 발행 : 2010.04.20
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초록

A rapid and sensitive reversed-phase high performance liquid chromatography (HPLC) method was developed for the determination of N-(-4-Chlorophenyl)-6-hydroxy-7-methoxy-2-chromanecarboxamide (KAL-1120), a novel anti-inflammation agent, in the rat plasma. The method was applied to analyze the compound in the biological fluids such as bile, urine and tissue homogenates. After liquid-liquid extraction, the compound was analyzed on an HPLC system with ultraviolet detection at 275 nm. HPLC was carried out using reversed-phase isocratic elution with a $C_{18}$ column, a mobile phase of a mixture of acetonitril (40 v/v%) at a flow rate of 1.0 mL/min. The chromatograms showed good resolution and sensitivity and no interference of plasma. The calibration curve for the drug in plasma was linear over the concentration range of 0.05-50 ${\mu}g$/mL. The intra- and inter-day assay accuracies of this method ranged from 0.06% to 9.33% of normal values and the precision did not exceed 6.28% of relative standard deviation. The plasma concentration of KAL-1120 decreased to below the quantifiable limit at 1.5 hr after the i.v. bolus administration of 2-10 mg/kg to rats ($t_{1/2,({\alpha})}$ and $t_{1/2,({\beta})$ of 2.15 and 26.7 min at a dose of 2 mg/kg, 3.91 and 33.0 min at a dose of 10 mg/kg, respectively). The steady-state volume of distribution ($V_{dss}$) and the total body clearance ($CL_t$) were not significantly altered in rats given doses from 2 to 10 mg/kg. Of the various tissues tested, KAL-1120 was mainly distributed in the lung and heart after i.v. bolus administration. KAL-1120 was detected in the bile by 30 min after its i.v. bolus administration. However, the concentration in the urine after i.v. bolus administration became too low to measure, suggesting that KAL-1120 is mostly excreted in the bile. In conclusion, this analytical method was suitable for the preclinical pharmacokinetic studies of KAL-1120 in rats.

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