Electrospary Tandem Mass를 이용한 혈중 글리퀴돈의 정량법 개발 및 생체이용률 시험

문철진(Chul-Jin Moon),이은희(Eun-Hee Lee),양송현(Song-Hyun Yang),문해란(Hae-Ran Moon) 대한약학회 2005 약학회지 Vol.49 No.3

A rapid, sensitive and selective electrospray tandem mass spectrometric (ESI-LC/MS/MS) method for the quantitation of gliquidone in human plasma was developed. A bioavailability study of gliquidone tablet (30 mg gliquidone, Boehringer Ingelheim Korea Co.) was performed using the validated ESI-LC/MS/MS method. The dose of 30 mg of gliquidone (1 tablet) was orally administered to 9 healthy Korean subjects. After administration, blood was taken at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 5, 7, 9, 12, 24, and 33 hour. The validation data were as follows; the standard curve was linear (γ2=0.999) over the concentration range of 10~1000 ng/ml. The coefficient of variation for intra- and inter-day assay were 8.30~18.86, and 2.19~12.92%, respectively. The lower limit of quantification for gliquidone was 10 ng/ml. The pharmacokinetic parameters obtained were as follows; AUCt was 3861.17±1328.61 ng.hr/ml, Cmax was 831.02±227.99 ng/ml, tmax was 2.94±0.77 hr, Ke was 0.19±0.06 1/hr, and t1/2 was 4.47±3.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of gliquidone dosage forms was prepared successfully and could be used for the bioequivalence test of gliquidone preparation.

Tandem Mass를 이용한 혈중 니코란딜의 정량법 개발 및 생체이용률시험

문철진(Chul-Jin Moon),이은희(Eun-Hee Lee),양송현(Song-Hyun Yang),문해란(Hae-Ran Moon) 대한약학회 2005 약학회지 Vol.49 No.3

A rapid, sensitive and selective tandem mass spectrometric method (LC-MS/MS) for the quantitation of nicorandil in human plasma was developed. A bioavailability study of Sigmat tablet(5 mg nicorandil, Choongwae Co.) was performed using the validated LC-MS/MS method. The dose of 5 mg of nicorandil (1 tablet) was orally administered to 9 healthy Korean subjects. After administration, blood was taken at 0.25, 0.5, 1, 2, 3, 4, 5, 6, 9, 12, and 24 hour. The validation data were as follows; the standard curve was linear (γ2=0.999) over the concentration range of 0.5~200.0 ng/ml. The coefficient of variation for intra- and inter-day assay were 3.55~7.44, and 2.17~9.10%, respectively. The lower limit of quantification for nicorandil was 0.5 ng/ml. The pharmacokinetic parameters obtained were as follows; AUCt was 145.9±83.0 ng.hr/ml, Cmax was 83.8±32.2 ng/ml, tmax was 0.42±0.13 hr, Ke was 0.56±0.23 1/hr, and t1/2 was 1.42±0.52 hr. Based on the validated analytical method and pharmacokinetic parameters, a standard guideline of the bioavailability test of nicorandil dosage forms was prepared successfully and could be used for the bioequivalence test of nicorandil preparation.

알루미늄을 투여한 흰쥐의 해마와 대뇌피질에서 Reactive Oxygen Species 생성으로 인한 생체거대분자의 산화적 손상

문철진(Chul-Jin Moon),고현철(Hyun-Chul Koh),신인철(In-Chul Shin),이은희(Eun-Hee Lee),문해란(Hae-Ran Moon) 한국독성학회 2004 Toxicological Research Vol.20 No.3

This work aimed to study the effectiveness of cellular oxidative parameter (malondialdehyde,<br/> protein carbonyl, and 8-hydroxy-2'deoxyguanosine). The experimental groups were aluminum<br/> treated rats and control rats. Aluminum treatd rats were given intraperitoneally aluminum nitrate<br/> nonahydrate (Al3+, 0.2 mmol/kg) daily for 30 days except Sunday. Control rats were injected 1 ml of<br/> saline. After the dose, rats were decapitated and hippocampus and cerebral cortex were removed.<br/> The measured parameters were tissue malondialdehyde (MDA, index of lipid peroxidation), protein<br/> carbonyl (index of protein oxidation), 8-hydroxy-2'-deoxy-guanosine (8-OHdG, index of DNA oxidation),<br/> reduced glutathione (GSH) levels as well as glutathione reductase (GR) and catalase. Al concentrations<br/> in the tissues were also measured. All results were corrected by tissue protein levels. The<br/> results were as followed; 1. The concentrations of Al in the cortex and hippocampus were significantly<br/> higher in the Al-treated rats than in the control rats. 2. Antioxidative enzyme's activity, catalase<br/> and GR, were significantly higher in the Al-treated rats than the control rats. GSH levels were also<br/> higher in the Al-treated rats. 3. MDA, protein carbonyl, and 8-OHdG concentration of Al-treated rats<br/> were significantly higher than those of control rats. 4. The concentrations of antioxidants, and oxidative<br/> stress parameter were correlated with the concentrations of Al in hippocampus and cerebral cortex.<br/> Catalase and GR activity were also correlated with the concentration of Al. Based on these<br/> results, it can be suggested that intraperitoneally injected Al was accumulated in the brain and<br/> induced the increase of antioxidant levels and antioxidatve enzyme activity. Also, the oxidative products<br/> of cellular macromolecules are significantly related to tissue Al concentration. Therefore MDA,<br/> protein carbonyl, and 8-OHdG are useful markers for oxidative stress on cellular macromolecules.

종합효소 연쇄반응을 이용한 비배양 객담에서의 Mycobacterium tuberculosis의 조기 검출

김성준(Sung-Joon Kim),김장성(Jang-Seong Kim),오달균(Dahl-Kyun Oh),문해란(Hae-Ran Moon),문홍모(Hong-Mo Moon) 大韓微生物學會 1993 大韓微生物學會誌 Vol.28 No.5

B 형 간염백신의 효과 - 접종부위에 따른 면역성의 차이 -

이창홍(Chang Hong Lee),박영태(Young Tae Park),유혜경(Hae Kyoung Yoo),이명석(Myung Seok Lee),문해란(Hae Ran Moon) 대한내과학회 1987 대한내과학회지 Vol.32 No.4

N/A The efficacy of a highly purified, formalin inactivated hepatitis B vaccine (Hepavax-B®), 20ug of surface antigen (HBsAg), given at 0, 1, and 6 months, was evaluated in 83 healthy young volunteers (mean age;25 years old) according to the injection sites of vaccine. All three doses had been given by arm injections in 51 subjects (A group) and the remainders (22 subjects) had received buttock injections for the first 2 doses followed by third-dose arm injections (B group). A significant decrease in seroconversion was noted 6 months after first dose injections in B group male subjects (31%) comparing with B group females and A group males and females, but conversion rate was rapidly elevated (95%) shortly after third-dose arm injections in these subjects. Geometrical mean antibody levels expressed as ratio units (RU) were significantly low 6 months after first dose injections in B group (both female % male) (p<0.005 vs. A group). This difference between A & B group was disappeared by the rapid increase of antibody level in B group subjects 2 months after third-dose injections, but in comparison with females, mean antibody level of male subjects was still significantly low in B group (p<0.005). Overall antibody conversion rates were over 95%, and antibody levels were above 10 RU in 90% of responders in both A & B groups 2 months after third-dose injections. Subjects with antibody levels above 100 RU were 65% in A group responders at the same time. In conclusion, as a method of hepatitis B vaccination, arm seems to be a superior site of injection to buttock even in young persons whose expected antibody responses are known to be excellent.

B 형 간염 바이러스에 의한 간질환에서 혈청 B 형 간염 바이러스 DNA 의 검출 양상

박영태(Young Tae Bak),이창홍(Chang Hong Lee),유혜경(Hae Kyoung Yoo),문해란(Hae Ran Moon),최규완(Kyoo Wan Choi),김경호(Kyong Ho Kim) 대한내과학회 1987 대한내과학회지 Vol.33 No.3

N/A Serum HBV-DNA was measured by spot hybridization technique in 189 cases with HBsAg positive acute and chronic liver diseases, HBV-DNA was detected in 62% (68/110) of HBeAg positive, in 16% (10f62) of anti-HBe positive, and in 18% (3/17) of both HBeAg and anti-HBe negative patients. Cases with higher levels of HBV-DNA among HBeAg positive patients were significantly more than those among the HBeAg negative patients, Among the HBeAg positive patients, HBV DNA was detected in 36% of AVH, 86% of healthy carriers, 63% of CPH, 62% of CAI-l-m, 58% of CAH-s, 65% of LC, and 71% of HCC. Among the HBeAg positive patients, those with histologically minimal or mild inflammatory change (healthy carrier, CPH, CAH-m) had higher levels of HBV-DNA, and those with histologically greater inflammatory or destructive change (CAH-s, LC, HCC, AVH) had lower levels of HBV-DNA. Above results suggest that detection of serum HBV- DNA in patients with HBV-related liver diseases may be useful to evaluate the degree of viral replication and infectivity and to predict the histological severity and relative prognosis.

국내 다제내성 결핵의 실태

김병주 ( Byoung Ju Kim ),이인희 ( In Hee Lee ),이덕형 ( Duk Hyung Lee ),배길한 ( Gill Han Bai ),공석준 ( Suk Jun Kong ),이선화 ( Sun Hwa Lee ),문해란 ( Hae Ran Moon ),이경률 ( Kyoung Ryul Lee ),이준영 ( Jun Young Lee ),박승규 ( Se 대한결핵 및 호흡기학회 2006 Tuberculosis and Respiratory Diseases Vol.60 No.4

목적 : 지난 3년간 전국적으로 항결핵제에 대한 감수성검사를 시행 받은 환자의 실제 수를 파악함으로 국내 다제내성 결핵의 현황을 파악하고자 하였다. 방법 : 2000년 1월부터 2002년 12월까지 3년간 국내의 결핵 약제감수성검사를 시행하고 있는 7개 국립 및 민간검사기관에서 시행된 검사결과들을 후향적으로 조사하여 이를 근거로 국내 결핵환자 중 다제내성 결핵환자의 연도별 현황 및 추이 등 다제내성 결핵 환자의 실제현황을 조사,분석하였다. 결과 : 6개의 검사기관은 절대농도법을 사용하였고 한 개의 기관에서 비율법을 사용하였다. 2000년부터 2002년까지 매년 18,071, 19,950, 그리고 21,919건의 검사가 시행되었다. 한 가지 이상의 약제에 내성으로 진단된 내성결핵 환자의 수는 2000년 6,338명에서 2002년 7,409명으로 16.9% 증가하였다. 약제감수성검사가 시행된 전체 환자들 중 내성결핵으로 진단된 환자의 비율은 2000년 35.1%, 2001년 34.5%, 그리고 2002년 33.8%이었다. 다제내성 결핵으로 확인된 환자는 2000년에 3,708명에서 2002년 4,245명으로 14.5%증가하였다. 결론 : 2002년에 약 4,000여건의 새로운 다제내성 결핵이 약제감수성검사에 의해 확인되었으며 매년 증가하는 경향을 보였다. 검사실간의 약제감수성검사의 표준화 작업과 보다 효과적인 다제내성 결핵의 관리가 요구 된다. Purpose : Multidrug-resistant tuberculosis (MDR-TB) is an emerging threat to human beings. However, there is little data on the current status of MDR-TB in Korea. This study investigated the current status of MDR-TB in Korea using a survey of all the data from drug susceptibility tests (DST) performed across the country over the last three years. Method : The DST results between Jan. 2000 and Dec. 2002 from 7 laboratories, which were in charge of all antituberculous DSTs across the country as of March 2002, were collected and analyzed to determine the actual number of drug-resistant or MDR-TB patients, annual trend, degree and pattern of resistance against anti-TB drugs, etc. Results : Six laboratories used the absolute concentration method for DST and one used the proportional method. 59,940 tests had been performed over the 3 year study period. The number of DST performed annually was 18,071, 19,950, and 21,919 in 2000-2002, respectively. The number of resistant tuberculosis patients (resistant against at least one anti-TB drug) had increased by 16.9% from 6,338 in 2000 to 7,409 in 2002. The rate of resistant tuberculosis among all DST results was 35.1% in 2000, 34.5% in 2001, and 33.8% in 2002. The number of MDR-TB patients (resistant against at least both isoniazid and rifampin) showed an increasing trend (14.5%) from 3,708 in 2000 to 4,245 in 2002. Conclusion : Approximately 4,000 MDR-TB cases are newly identified by DST annually and the number is showing an increasing trend. This study suggests that in order to cope with the current MDR-TB situation, the DST methods will need to be standardized and more aggressive measures will be required. (Tuberc Respir Dis 2006; 60: 404-411)

정도관리 총오차의 최소화 방법에 대한 연구

장상우 ( Sang Wu Chang ),장석배 ( Seok Bae Chang ),김완 ( Wan Kim ),서한익 ( Han Ik Sur ),임용현 ( Yong Hyeon Rim ),김남용 ( Nam Yong Kim ),이은희 ( Eun Hee Lee ),문해란 ( Hae Ran Moon ),김용호 ( Yong Ho Kim ),조영주 ( Young Ju C 대한임상검사과학회 1994 대한임상검사과학회지(KJCLS) Vol.26 No.1