혈장, 뇨 및 조직 중 JAK 억제제인 tofacitinib의 HPLC분석법 및 약물동력학 연구에의 적용

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dc.contributor.advisor김소희, 김수동-
dc.contributor.author김지은-
dc.date.accessioned2019-10-21T07:32:06Z-
dc.date.available2019-10-21T07:32:06Z-
dc.date.issued2018-02-
dc.identifier.other27639-
dc.identifier.urihttps://dspace.ajou.ac.kr/handle/2018.oak/19255-
dc.description학위논문(석사)--아주대학교 글로벌제약임상대학원 :글로벌제약임상약학과,2018. 2-
dc.description.tableofcontentsI.INTRODUCTION 1 II.METHOD 4 A.Chemicals 4 B.Animals 4 C.Preparation of standard solutions 4 D.Sample preparations 5 E.HPLC apparatus 6 F.Method validation 6 G.Stability studies 8 H.Pharmacokinetic studies 10 I.Statistical analysis 11 III.RESULTS 12 A.Validation of HPLC method 12 B.Stability studies 23 C.Pharmacokinetic studies 25 IV.DISCUSSION 28 V.CONCLUSION 30 REFERENCES 31 KOREAN ABSTRACT 35-
dc.language.isoeng-
dc.publisherThe Graduate School, Ajou University-
dc.rights아주대학교 논문은 저작권에 의해 보호받습니다.-
dc.title혈장, 뇨 및 조직 중 JAK 억제제인 tofacitinib의 HPLC분석법 및 약물동력학 연구에의 적용-
dc.title.alternativeSimple determination of tofacitinib, a JAK inhibitor, in plasma, urine and tissue homogenates by HPLC and its application to a pharmacokinetic study-
dc.typeThesis-
dc.contributor.affiliation아주대학교 글로벌제약임상대학원-
dc.contributor.alternativeNameKim jieun-
dc.contributor.department글로벌제약임상대학원 글로벌제약임상약학과-
dc.date.awarded2018. 2-
dc.description.degreeMaster-
dc.identifier.localId800809-
dc.identifier.urlhttp://dcoll.ajou.ac.kr:9080/dcollection/jsp/common/DcLoOrgPer.jsp?sItemId=000000027639-
dc.subject.keywordHPLC-
dc.subject.keywordtofacitinib-
dc.subject.keywordLLOQ-
dc.subject.keywordprecision-
dc.subject.keywordaccuracy-
dc.subject.keywordpharmacokinetics-
dc.description.alternativeAbstractTofacitinib, a janus kinase inhibitor, was developed to treat rheumatoid arthritis. To evaluate its pharmacokinetic characteristics, a simple high-performance liquid chromatography method was developed to determine the tofacitinib levels in rat plasma, urine, and tissue homogenates using hydrocortisone as an internal standard. The mobile phase was an isocratic system of 10 mM ammonium acetate : acetonitrile = 69.5:30.5 at a flow rate of 1.0 mL/min. Chromatograms were monitored by an ultraviolet detector at 287 nm. The retention times for tofacitinib and hydrocortisone were 6.93 and 11.0 min, respectively, and the lower limits of quantification for tofacitinib in rat plasma and urine were 0.01 and 0.1 g/mL, respectively. The intra-day assay precision values (coefficients of variation) were generally low, in the ranges of 3.69–5.88% and 4.21–6.18% for rat plasma and urine, respectively; the corresponding inter-day assay precision values were 5.06 and 5.46%, also respectively. The accuracies (relative errors) ranged from 89.5 to 111%. No interference from endogenous substances was found. An initial pharmacokinetic study was performed in Sprague-Dawley rats and demonstrated that tofacitinib has a short half-life (39.0 min) and wide tissue distribution. In summary, this HPLC method can be applied to future preclinical and clinical investigations of tofacitinib.-
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