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Tranylcypromine 광학이성질체에 의한 MAO 자살억제의 반응속도론
강건일(Gun Il Kang),최명희(Myung Hee Choi) 대한약학회 1989 약학회지 Vol.33 No.1
Since time-dependent inactivation of MAO was found to be complete in a few minutes when high concentration ratios of tranylcypromine to MAO were used, a method to obtain kinetic parameters was sought suitable to the conditions in which concentrations of tranylcypromine analogs did not exceed that of MAO. For the purpose, kinetic equations were derived and the method applied to the kinetic studies of tranylcypromine enantiomers. It was found that (E)-(+)-2-phenylcyclopropylamine inhibited MAO by the mechanism following bimolecular reaction scheme with KI of 2.0 X 106M-1min-1. Whereas, MAO-inhibitory pattern of the (-)-enantiomer was to be interpreted by suicide inhibition scheme and measured kin and K'' were 0.457min-1 and 5.4mcM, respectively.
Methadone 의 Biotransformation 과정중 N - Hydroxy Metabolite 의 생성가능성에 대한 질량 분석학적 증거
강건일 ( Gun Il Kang ) 생화학분자생물학회 1983 BMB Reports Vol.16 No.1
The deuterium labeled methadone and metabolites were used for GCMS (Gas Chromatography Mass Spectrometry) detection and identification of methadone metabolites. The conjugated fraction from methadone dosed rat bile was found to contain a new m/z 72 containing compound. On the basis of GCMS data the new compound was assigned as normethadone nitrone (N-methylene-1-methyl-3, 3-diphenyl-4-oxo-hexanamineoxide). The nitrone appears to result from decomposition of N-hydroxynormethadone during sample preparation procedures. Possibilities for the metabolic formation of N-hydroxynormethadone and its physiological significance were discussed.
GC-FID에 의한 Rat 뇨중 Tranylcypromine의 분석
강건일(Gun Il Kang),정순영(Soon Young Chung) 대한약학회 1985 약학회지 Vol.29 No.5
A gas chromatography with flame ionization detection was developed to measure tranylcypromine in rat urine. The method involves extraction of the drug and the internal standard, N-methyl-3-phenylpropylamine from the urine using ethyl acetate and back extraction into 0.5N H2SO4. Following final extraction using dichloromethane, both the drug and the internal standard were converted to trifluoroacetyl derivatives and analyzed using a column of 3% SE-30 on 80/100 mesh Chromosorb W(HP). A calibration curve was constructed in the range of 5~50mcg tranylcypromine sulfate in 0.5ml urine and found to be linear. The detection limit was 2mcg. The tranylcypromine could be analyzed with the percent recovery of 100.81 +/- 8.13 (SD) in a concentration range of 8~40mcg in 0.5ml urine. When 0.4mmol/kg dose of the drug was administered through an oral route, excretion percent of tranylcypromine in rat urine over 36 hr was found to be 11.90 +/- 6.04 (SD) for tranylcypromine sulfate and 2.23 +/- 0.63 (SD) for benzyl trans-2-phenylcyclopropanecarbamate.
Tranylcypromine의 겉보기 해리항수(解離恒數) 및 분배계수(分配係數)
강건일,정순영,Kang, Gun-Il,Chung, Soon-Young 대한약학회 1984 약학회지 Vol.28 No.5
The pKa' of tranylcypromine was determined by potentiometric titration and ultraviolet spectrophotometric method and found to be 8.08 and 8.15, respectively. The Papp of tranylcypromine between n-heptane and aqueous buffer solution was measured to be 0.90 at pH 7.48 and 4.50 for Pm. The pKa' of tranylcypromine obtained by means of the partition method was 8.13.
Mass Spectrometric Evidence for N-Hydroxy Metabolic Pathway of Methadone
강건일,Kang, Gun-Il 생화학분자생물학회 1983 한국생화학회지 Vol.16 No.1
Methadone 대사물질의 GCMS 검출 및 확인을 위하여 중수소로 치환된 methadone 및 그 대사물질을 이용하였다. methadone을 투여한 쥐에서 얻은 bile의 conjugate fraction에서 m/z 72를 함유한 물질을 검출하였고 GCMS data를 근거로 하여 normethadone nitrone (N-methylene-1-methyl-3, 3-diphenyl-4-oxo-hexanamine-oxide)으로 확인하였다. 이 물질은 sample 처리과정에서 생긴 N-hydroxynormethadone의 분해 산물로 추청된다. N-hydroxynormethadone의 대사에 의한 생성 가능성 및 그 중요성을 기술하였다. The deuterium labeled methadone and metabolites were used for GCMS (Gas Chromatography Mass Spectrometry) detection and identification of methadone metabolites. The conjugated fraction from methadone dosed rat bile was found to contain a new m/z 72 containing compound. On the basis of GCMS data the new compound was assigned as normethadone nitrone (N-methylene-1-methyl-3, 3-diphenyl-4-oxo-hexanamineoxide). The nitrone appears to result from decomposition of N-hydroxynormethadone during sample preparation procedures. Possibilities for the metabolic formation of N-hydroxynormethadone and its physiological significance were discussed.
흰쥐 간 Microsome효소에 의한 Tranylcypromine으로부터 Cinnamaldehyde의 생성
홍석길(Suk Kil Hong),강건일(Gun Il Kang) 大韓藥學會 1990 약학회지 Vol.34 No.3
In order to clarify mechanism of the formation of cinnamaldehyde(CNA) in incubation mixtures of tranylcypromine(TCP) with rat liver microsomes, the CNA formed under various incubation conditions were analyzed. For the purpose, HPLC method of the analysis of CNA was developed. The formation of CNA was found to be dependent on the incubation time and the amounts of microsomes added. In addition, exclusion of NADPH or NADP of NADPH-generating system in incubation mixtures resulted in the formation of markedly decreased amounts of CNA to 8.5 and 2.4%, respectively, relative to the amounts formed each in a standard system. The small amounts measured were comparable to those formed by incubation without microsomes or with boiled microsomes. The results clearly Suggested that CNA is a metabolic product of TCP by rat liver microsomes though further studies are needed to Suggest details of the steps to the formation of CNA from TCP and of the enzymatic entities involved in the formation of CNA.
강건일 한국약제학회 1984 Journal of Pharmaceutical Investigation Vol.14 No.4
The use of stable isotope compounds in pharmaceutical research was described with recent 33 references, which include synthesis, selected ion monitoring, pharmacokinetics, drug metabolism, and mechanism of drug action.
이상희,김용배,김건치,강건일 한국약제학회 1972 Journal of Pharmaceutical Investigation Vol.2 No.1
The stabillities of taurine, niacinamide, and pyridoxine hydrochloride under exposure to ultra violet radiation in liquid preparations were studied. And sterilization effects for E. coli in both water and liquid preparations were also comparatively evaluated. The above mentioned organic compounds were stable under this experimental conditions and viable count of E. coli reveals that organic compounds dissolved in solution display protective action for microorganisms under UV-irradiation.