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원보 : LC/MS/MS를 이용한 비글견의 혈장 중 Doxifluridine 및 5-Fluorouracil의 동시 분석법 Validation
김기환 ( Ghee Hwan Kim ),김원 ( Won Kim ),김진성 ( Jin Sung Kim ),김경일 ( Qing Ri Jin ),강원구 ( Won Ku Kang ),이종화 ( Jong Hwa Lee ),하정헌 ( Jung Heun Ha ),정은주 ( Eun Ju Jeong ) 한국약제학회 2007 Journal of Pharmaceutical Investigation Vol.37 No.3
LC/MS/MS를 이용한 원숭이 및 비글견의 간 및 장관 조직에서의 Doxifluridine과 대사체 5-FU 동시분석법 개발
우영아,김기환,정은주,김충용,Woo, Young-Ah,Kim, Ghee-Hwan,Jeong, Eun-Ju,Kim, Choong-Yong 대한약학회 2008 약학회지 Vol.52 No.2
A liquid chromatographic method with tandom spectrometric detection (LC/MS/MS) for the simultaneous determination of doxifluridine and its active metabolite, 5-fluorouracil (5-FU) was developed over the concentration range of $5{\sim}2000$ ng/ml, respectively. Doxifluridine, 5-FU and internal standard, 5-chlorouracil (5-CU), were extracted from liver and intestine tissue via protein precipitation. Acetonitrile was used as the extraction solvent and the supernatant was evaporated and reconstructed in mobile phase. Optimum chromatographic separation was achieved on a Agilent Zorbax $C_{18}$ ($100\;mm{\times}2.1\;mm$, $3.5\;{\mu}m$) column with mobile phase run in isocratic with methanol : water (20 : 80, v/v). The flow rate was 0.2 ml/min with total cycle time of 5 min. The lower limit of quantification was validated at 5.0 ng/ml of liver and intestine tissue, for both doxifluridine and 5-FU, respectively. The intra-day and inter-day precision and accuracy of quality control (QC) samples were <11% coefficient of variation and <7% relative error from theoretical concentration for both analytes. In addition, the special designed stability study was performed, because the metabolism of doxifluridine occurs spontaneously even in ice bath for monkey liver. The stability of doxifluridine in liver and intestine of monkey and beagle dog was compared. It was found that bioanalytical validation could not be performed for the monkey liver; however, beagle dog's liver has relatively low speed of metabolism compared to monkey liver and instead of monkey liver, beagle dog's liver could be used for the validation. Bioanalytical validation could be performed in monkey intestine. Eventually, this developed method for liver and intestine will be useful in support of the toxicokinetic and pharmacokinetic studies of doxifluridine and 5-FU.
LC/MS/MS를 이용한 원숭이 혈액에서의 Doxifluridine과 대사체 5-FU 동시분석법 개발 및 Validation
우영아,김기환,김원,이종화,정은주,김진호,박귀례,김충용,Woo, Young-Ah,Kim, Ghee-Hwan,Kim, Won,Lee, Jong-Hwa,Jeong, Eun-Ju,Kim, Jin-Ho,Park, Kui-Lea,Kim, Choong-Yong 대한약학회 2007 약학회지 Vol.51 No.3
A reverse-phase high performance liquid chromatography method with electrospray ionization and detection by mass spectrometry is described for the simultaneous determination of doxifluridine and its active metabolite 5-flu-orouracil (5-FU) in monkey serum. The method has greater sensitivity and simpler process than previous published methods with good accuracy and precision. A proper liquid/liquid extraction was used to extract simultaneously doxifluridine and 5-FU which has considerable difference in the polarity. Extracts were analyzed using LC/MS/MS providing a short analysis time within 5 min. The lower limit of quantification was validated at 10.0 ng/ml of serum for both doxifluridine and 5-FU. Accuracy and precision of quality control (QC) samples for both analytes met FDA Guidance criteria of ±15% for average QC accuracy with coefficients of variation less than 15%. The method will be applicable for preclinical studies and bioequivalence studies.
Chrysene이 BALB/c계 마우스의 면역기능에 미치는 영향
전태원,김춘화,이상규,김기환,전인혜,이동주,정혜민,정태천,Jeon, Tae-Won,Kim, Chun-Hua,Lee, Sang-Kyu,Kim, Ghee-Hwan,Jun, In-Hye,Lee, Dong-Ju,Jeong, He-Min,Jeong, Tae-Cheon 대한약학회 2006 약학회지 Vol.50 No.4
Effects of chrysene on immune functions were studied in female BALB/c mice. When mice were treated po with chrysene for 7 consecutive days, the antibody response was suppressed dose-dependently. Chrysene induced the enzyme activities of CYP LA and 2B time- and dose-dependently. In ex vivo lymphocyte proliferation, chrysene inhibited splenocyte proliferation by LPS and Con A. Moreover, the numbers of $CD4^+IL-2^+$ cells were reduced by chrysene. In conclusion, chrysene-induced immunotoxicity might be mediated, at least in part, via IL-2 production, and caused by mechanisms associated with metabolic activation.
소아 잠복 결핵 감염 진단에 있어서 투베르쿨린 피부반응 검사와 결핵 특이항원 자극 Interferon-γ 분비능 측정의 비교
전진경,김창기,김현숙,정귀영,인요한,김기환,이택진,전지현,김동수,Chun, Jin-Kyong,Kim, Chang Ki,Kim, Hyun Sook,Jung, Ghee Young,Linton, John A.,Kim, Ki Hwan,Lee, Taek Jin,Jeon, Ji Hyun,Kim, Dong Soo 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.9
목 적 : 결핵 감염 관리에 있어서 잠복 결핵 감염을 찾아 내어 예방적 화학요법을 시행하는 것은 주요 핵심이다. 결핵에 노출된 소아에서 잠복 결핵 감염 진단을 위해 투베르쿨린 피부반응과 최근 널리 쓰이기 시작한 체외 검사법으로 결핵 특이항원 자극에 의한 T 세포의 $IFN-{\gamma}$ 분비능 측정 (QFT-G IT)이 있다. 잠복 결핵 감염 진단에 있어 두 검사법의 차이를 알아보고자 본 연구를 진행하였다. 방 법 : 2006년 10월 1일부터 2007년 4월 30일까지 6개월 간 총 111명의 소아를 대상으로 투베르쿨린 반응과 QFT-G IT 검사를 시행하였고, 동일 기간 내인 2개월 간 진단 된 성인 결핵 환자 29명에서 동일한 검사 결과를 후향적으로 알아보았다. 결 과 : 결핵 환자와의 가까운 접촉력을 주소로 내원한 무증상의 환자 33명 중 15% (5명)에서 QFT-G IT 검사 양성 소견을 보였고, 투베르쿨린 피부반응은 42% (14명)에서 양성결과를 보여 두 검사 간의 일치율은 낮았다(${\kappa}=0.39$). 성인 결핵 환자에서 QFT-G IT 양성율은 86.2%였고, 결핵균 배양 검사 양성율은 48.2%였다. 배양검사 양성이면서 QFT-G IT 음성이었던 환자는 12.5%였다. 결 론 : 소아에서 잠복 결핵 감염을 진단함에 있어 가족력을 근저에 둔 투베르쿨린 피부반응 검사를 시행하되 접촉력이 불분명하거나 지속적이지 않았을 경우 혹은 BCG 접종 효과로 의심되는 경우 결핵균 특이항원 자극 $IFN-{\gamma}$ 분비능 측정이 보조적 수단으로 사용 될 수 있을 지는 아직 확실하지 않으며 향후 수년 간 다 기관 연구가 필요하다. Purpose : Surveillance for detecting and managing latent tuberculosis infection (LTBI) is a key component of tuberculosis control. The classic surveillance tool, the tuberculin skin test (TST), may have some limitations when used in the Bacillus Calmette-$Gu{\acute{e}}rin$ (BCG)-vaccinated population. The object was to perform a blood test $QuantiFERON^{(R)}$-TB Gold In Tube (QFT-G IT) based on the detection of interferon-$\gamma$ ($IFN-{\gamma}$) released by T cells in response to Mycobacterium tuberculosis-specific antigens, and to compare the efficacy of this new diagnostic tool for LTBI with that of TST. Methods : For six months, between October 1, 2006 and April 30, 2007, data were collected from 111 patients under 15 years of age at Severance Children's Hospital. TST and QFT-G IT tests were performed with children with or without contact histories of tuberculosis. In addition to these tests, we examined comparative data from 29 adults who had tuberculosis, to detect false negative rates in the QFT-G IT method. Results : Thirty-three children had household contact histories. In this group, 15% and 42% of cases were found to be positive using the QFT-G IT assay and TST, respectively. Agreement was low between these two tests (${\kappa}=0.39$). In the adult active tuberculosis group, the QFT-G IT false negative rate defined as a positive culture and a negative QFT-G IT result was 12.5%. Conclusion : In diagnosing LTBI in children, the usefulness of a whole-blood $IFN-{\gamma}$ assay employing TB-specific antigens will be revealed only by examining additional longitudinal clinical data; this study serves as a starting point in that process.
연구논문 : 생명과학 ; 질량분석을 이용한 1,2-dibromopropane의 글루타치온 포합체 생성 및 구조 규명에 관한 연구
이상규 ( Sang Kyu Lee ),김춘화 ( Chun Hua Jin ),현선희 ( Sun Hee Hyun ),이동욱 ( Dong Wook Lee ),김기환 ( Ghee Hwan Kim ),전태원 ( Tae Won Jeon ),이재익 ( Jae Ick Lee ),김동현 ( Dong Hyun Kim ),정혜광 ( Hye Gwang Jeong ),이응석 ( 영남대학교 약품개발연구소 2005 영남대학교 약품개발연구소 연구업적집 Vol.15 No.-
약학박사 정 시련 교수 정년퇴임 기념호 : 연구논문(재록) ; 생명과학 : Rutaecarpine의 면역독성 연구
전태원 ( Tae Won Jeon ),김춘화 ( Chun Hua Jin ),이상규 ( Sang Kyu Lee ),전인혜 ( In Hye Jun ),김기환 ( Ghee Hwan Kim ),이동주 ( Dong Ju Lee ),정혜광 ( Hye Gwang Jeong ),이경복 ( Kyung Bok Lee ),장영동 ( Yurng Dong Jahng ),정태천 ( 영남대학교 약품개발연구소 2006 영남대학교 약품개발연구소 연구업적집 Vol.16 No.-
약학박사 정 시련 교수 정년퇴임 기념호 : 연구논문(재록) ; 생명과학 : 마우스에서 2,3-dibromopropene의 glutathione 포합체 확인에 관한 연구
이상규 ( Sang Kyu Lee ),백서연 ( Seo Yeon Baik ),전태원 ( Tae Won Jeon ),전인혜 ( In Hye Jun ),김기환 ( Ghee Hwan Kim ),김춘화 ( Chun Hua Jin ),이동주 ( Dong Ju Lee ),김준규 ( Jun Kyou Kim ),염영나 ( Young Na Yum ),정태천 ( Tae Ch 영남대학교 약품개발연구소 2006 영남대학교 약품개발연구소 연구업적집 Vol.16 No.-
약학박사 정 시련 교수 정년퇴임 기념호 : 연구논문(재록) ; 생명과학 : 질량분석을 이용한 rutaecarpine의 phase 2 대사체 규명
이상규 ( Sang Kyu Lee ),이동욱 ( Dong Wook Lee ),전태원 ( Tae Won Jeon ),김춘화 ( Chun Hua Jin ),김기환 ( Ghee Hwan Kim ),전인혜 ( In Hye Jun ),이동주 ( Dong Ju Lee ),김승일 ( Seung Il Kim ),김동현 ( Dong Hyun Kim ),장영동 ( Yurng 영남대학교 약품개발연구소 2006 영남대학교 약품개발연구소 연구업적집 Vol.16 No.-
약학박사 정 시련 교수 정년퇴임 기념호 : 연구논문(재록) ; 생명과학 : 1-Bromopropane의 간독성 및 glutathione 포합
이상규 ( Sang Kyu Lee ),조상욱 ( Sang Wook Jo ),전태원 ( Tae Won Jeon ),전인혜 ( In Hye Jun ),김춘화 ( Chun Hua Jin ),김기환 ( Ghee Hwan Kim ),이동주 ( Dong Ju Lee ),김태오 ( Tae Oh Kim ),이응석 ( Eun Seok Lee ),정태천 ( Tee Cheon 영남대학교 약품개발연구소 2006 영남대학교 약품개발연구소 연구업적집 Vol.16 No.-