• 분석과학
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• 제17권4호
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• pp.337-346
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• 2004

근육강화제의 일종인 7-keto-dehydroepiandrosterone-acetate (7-keto-DHEA-acetate)를 투여시킨 후 사람의 뇨를 통해서 배설되는 대사체들을 확인하고 그 결과를 향후 도핑 검사에 있어서 금지 약물로 선정될 경우를 대비한 기초 연구를 진행하고자 하였다. 먼저 뇨 시료의 매트릭스로부터 7-keto-DHEA-acetate가 방해 없이 효과적으로 검출되는 것을 알아보았으며, 약물을 복용한 dosed urine에 배설되는 대사체를 검출하기 위하여 LC/ESI/MS와 GC/MSD를 사용하였다. 그 결과 바탕 뇨 시료에서 나타나지 않은 여러 개의 새로운 화합물들이 복용 뇨 시료에서 검출되었으며 이들을 M1, M2, M3, M4 및 M5로 구별 하였으며 이 결과들로부터 대사체 M1과 M2는 물분자가 제거될 수 있는 히드록시기나 케톤기를 세 개 이상 가진 구조일 것으로 예상되었다. M1의 경우, m/z 518 이 분자이온이라면 분자량이 302인 이 대사체는 3번과 17번 탄소 위치에 케톤기, 7번 탄소위치에서 히드록시기를 가지는 구조인 7-OH-androstendione이라고 예상 할 수 있었으며, M2의 경우에는 M1 대사체와 마찬가지로 m/z 518이 분자이온이라면 분자량이 302인 이 대사체는 3번 탄소 위치에 히드록시기가 있고 17번 탄소 위치에 케톤기를 가지며 7번 탄소위치에 케톤기가 있는 구조인 7-keto-DHEA로 판단되었다.

• 약학회지
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• 제36권3호
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• pp.230-240
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• 1992

The metabolic profile of doxylamine, N,N-dimethyl-2-[1-phenyl-1-(2-pyridinyl)ethoxy] ethanamine, was determined in the human urine. The free fractions of extracts were obtained without hydrolysis, and the conjugated fractions of extracts were obtained with enzyme hydrolysis using ${\beta}-glucuronidase/arylsulfatase$ from Helix pomatia. The mixture of acetic anhydride/pyridine (10 : 1, v : v) was used to derivatize the urinary extracts and then analyzed by gas chromatography and mass selective detector. N-desmethyldoxylamine, doxylamine carboxylic acid, desaminohydroxydoxylamine, N, N-didesmethyldoxylamine, N-acetyl conjugates of N-desmethyl and N, N-didesmethyldoxylamine, quarternary ammonium N-glucuronide of doxylamine, N-desmethyldoxylamine N-glucuronide and unchanged doxylamine were detected in the human urine obtained after oral treatment with doxylamine succinate. $N-methyl-{\alpha}-hydroxy-2-[1-phenyl-1-(2-pyridinyl)$ ethoxy] ethanamine, which can be a key intermediate of this metabolism, was tentatively identified by the interpretation of its mass spectrum. In this study, we proposed the metabolic pathway of doxylamine in the human on the basis of our data of the identified metabolites of doxylamine.

• 한국산업보건학회지
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• 제9권2호
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• pp.100-109
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• 1999

This study evaluates the pretreatment for analysis of benzidine metabolites in urine by measuring the recovery rates according to the temperature and periods of storage of the urine. By the solid phas e extraction, the recovery rates of basic hydrolysis are benzidine 67.4 %, monoacetylbenzidine 105.1 %, and diacetylbenzidine 115.8 %, respectively. By the liquid extraction, the recovery rates of back-extraction into 0.1 M perchloric acid are benzidine 105.7%, monoacetylbenzidine 94.2 %, diacetylbenzidine 72.8 %, respectively. The difference of the recovery rates between the back-extraction into 0.1 M HCl and 0.1 M perchloic acid after basic hydrolysis are 101 % and 98.8 %, respectively. When the recovery rates of the urinary s amples of pH 3, pH 7, pH 12 at $25^{\circ}C$ and $-76^{\circ}C$ are compared for four weeks, there are no differences according to the temperature and the periods of storage. The above results show that the solid phase extraction and back-extraction by 0.1 M perchloric acid after basic hydrolys is are suitable for the analysis of benzidine metabolites. There are no difference of the recovery rates of the urinary samples stored at $25^{\circ}C$ and $-76^{\circ}C$ at pH 3, pH 7, pH 12, respectively for 28 days.

• Archives of Pharmacal Research
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• 제25권5호
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• pp.709-717
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• 2002

Hypoxemia is known to induce various physiological changes which can result in alteration in drug pharmacokinetics. To examine the effect of acute moderate hypoxemia on metoclopramide (MCP) pharmacokinetics, a continuous 14-hour infusion of MCP during a normoxemic, hypoxemic and subsequent normoxemic period was conducted in eight adult sheep. Arterial blood and urine samples were collected to examine the effects on the pharmacokinetics of MCP and its deethylated metabolites. MCP and its mono- and di-deethylated metabolites were quantitated using a GC/MS method. Steady-state concentrations of MCP were achieved in each of the three periods. During hypoxemia, MCP plasma steady-state concentration increased significantly from 50.72$\pm$1.06 to 63.62$\pm$1.79 ng/mL, and later decreased to 55.83$\pm$1.15 ng/mL during the post-hypoxemic recovery period. Total body clearance ($CL_{TB}$) of MCP was significantly decreased from 274.2$\pm$48.0 L/h to 205.40$\pm$28.2 L/h during hypoxemia, and later restored to 245.8$\pm$44.2 L/h during the post-hypoxemic period. Plasma mono-deethylated MCP concentration (32.78$\pm$1.73 ng/mL) also increased, compared to the control group (21.20$\\pm$1.39 ng/mL), during hypoxemia and subsequent normoxemic period. Renal excretion of MCP and its metabolites was also decreased during hypoxemia, while urine flow was increased with a concomitant decrease in urine osmolality. Thus, the results indicate that acute moderate hypoxemia affects MCP pharmacokinetics.

• Bulletin of the Korean Chemical Society
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• 제32권4호
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• pp.1158-1164
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• 2011

5-Methoxy-N,N-diisopropyltryptamine (5-MeO-DIPT), a psychoactive tryptamine derivative, is a hallucinogenic drug of abuse. In this study, 5-OH-DIPT and its metabolites were identified and the quantitative method was developed and validated by using hydrophilic interaction chromatography-tandem mass spectrometry (HILICMS/MS). Chromatographic separation was achieved on an Atlantis HILIC silica column ($5{\mu}m$, $100{\times}2.1\;mm$). The metabolites of 5-MeO-DIPT in rat urine were characterized via Q1 scanning and product ion scanning. As a consequence, 5-MeO-IPT, 5-OH-DIPT, 6-OH-5-MeO-DIPT and their glucuronide conjugates were detected and identified as the metabolites of 5-MeO-DIPT. Subsequently, a quantitative method for 5-MeO-DIPT and its major metabolites, 5-MeO-IPT and 5-OH-DIPT, was developed in multiple reactions monitoring (MRM) mode. The calibration curves for all analytes evidenced good linearity over the concentration range of 1-1000 ng/mL with linear correlation co-efficients ($r^2$) in excess of 0.99. The intra- and inter-day accuracy and precision were 92.2-110.2% and 1.5-9.9%, respectively.

• 분석과학
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• 제13권2호
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• pp.258-267
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• 2000

1995년부터 실시해 온 산업보건 분야의 '유해물질 및 대사물 분석의 실험실간 정도관리 프로그램'(공식명: 특수건강진단기관 분석정도관리)의 5년간 실시 경과와 결과를 보고하고, 고찰을 통하여 우리나라 산업보건분야 실험실 서비스의 질관리를 위한 앞으로의 방향 등을 제시하고자 한다. 산업현장에서 많이 쓰이는 4가지 혈중 중금속과 5가지 유기용제 대사물에 대하여 연구원에서 제조된 표준시료를 분배하고 결과 분석값과 크로마토그람 등 관련 자료들을 분석하여 참가기관에 대한 분석능력 평가를 실시하였다. 연 2회 실시된 정도관리 결과는 인터넷 등을 통하여 고시하여 산업보건 관련 실험실들의 자율적인 질관리 서비스 경쟁을 유도하고, 관련 실험실 서비스의 사용자인 근로자, 사업주, 산업보건 관련자들의 알 권리를 충족시켜, 실험실의 분석데이타에 대한 객관적인 신뢰도를 확보하고 산업보건 서비스의 질 향상에 크게 기여하였다.

• 한국식품위생안전성학회지
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• 제18권3호
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• pp.153-160
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• 2003

Methidation을 흰쥐에 경구투여 및 피부도포 후 뇨 중 대사물질을 GC/MS로 분석하였고, 투여경로에 따른 뇨 중 대사물질의 차이를 비교하였으며, 뇨 중 dialkyl phosphte의 시간별 배설량과 그 외 대사물질을 측정하여 다음과 같은 결과를 얻었다. Methidathion을 경구투여 및 피부도포 후 뇨 중 대사물질을 측정한 결과 유기인계 농약의 공통적인 대사물질인 dialkyl phosphtes 중 세 가지 물질인 DMP, DMTP 및 DMDTP로 동일하게 배설되었다. GC/MS로 주요조각이온을 확인한 결과 DMP는 m/z=153, 127, 109, DMTP는 m/z=198, 142, 109 그리고, DMDTP는 m/z-158, 125, 93에서 분자이온을 확인할 수 있었다. Methidathion을 경구투여 및 피부도포 후 뇨 중 dialkyl phosphtes의 시간별 배설량을 측정한 결과 경구투여의 경우 DMP는 12시간 이내에 79.2%, DMTP는 24시간 이내에 93.3% 그리고, DMDTP는 12시간 이내에 83.0%가 배설되었고, 피부도포의 경우 DMP는 24시간 이내에 71.1%, DMTP와 DMDTP는 48시간 이내에 각각 82.8%, 87.7%가 배설되었다. 이 결과 경구투여 한 실험에서는 48시간 이내에 뇨 중 dialkyl phosphtes가 완전히 배설되는 반면 피부도포 한 실험에서는 각 개체의 상태에 따라 대사물질들이 늦게는 168시간까지 배설이 지연됨을 알 수 있었다. 이상의 결과를 종합하면, 흰쥐에 methidathion을 경구투여 및 피부도포 후 뇨 중 대사물질을 측정한 결과 dialkyl phosphate 중 DMP, DMTP로 검출되었으며, 경구 투여와 피부도포 시 뇨 중 대사물질의 차이는 없었으나, 경구투여보다 피부도포의 경우 배설이 더 지연되었다. 결론적으로, methidathion의 뇨 중 대사물질인 DMP, DMTP 및 DMDTP는 이 농약의 생체모니터링 지표물질로서 사용될 수 있을 것으로 생각된다.

• Asian-Australasian Journal of Animal Sciences
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• 제30권11호
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• pp.1633-1642
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• 2017

Objective: Evaluation of exercise effects in racehorses is important in horseracing industry and animal health care. In this study, we compared metabolic patterns between before and after exercise to screen metabolic biomarkers for exercise effects in thoroughbreds. Methods: The concentration of metabolites in muscle, plasma, and urine was measured by $^1H$ nuclear magnetic resonance (NMR) spectroscopy analysis and the relative metabolite levels in the three samples were compared between before and after exercise. Subsequently, multivariate data analysis based on the metabolic profiles was performed using orthogonal partial least square discriminant analysis (OPLS-DA) and variable important plots and t-test was used for basic statistical analysis. Results: From $^1H$ NMR spectroscopy analysis, 35, 25, and 34 metabolites were detected in the muscle, plasma, and urine. Aspartate, betaine, choline, cysteine, ethanol, and threonine were increased over 2-fold in the muscle; propionate and trimethylamine were increased over 2-fold in the plasma; and alanine, glycerol, inosine, lactate, and pyruvate were increased over 2-fold whereas acetoacetate, arginine, citrulline, creatine, glutamine, glutarate, hippurate, lysine, methionine, phenylacetylglycine, taurine, trigonelline, trimethylamine, and trimethylamine N-oxide were decreased below 0.5-fold in the urine. The OPLS-DA showed clear separation of the metabolic patterns before and after exercise in the muscle, plasma, and urine. Statistical analysis showed that after exercise, acetoacetate, arginine, glutamine, hippurate, phenylacetylglycine trimethylamine, trimethylamine N-oxide, and trigonelline were significantly decreased and alanine, glycerol, inosine, lactate, and pyruvate were significantly increased in the urine (p<0.05). Conclusion: In conclusion, we analyzed integrated metabolic patterns in the muscle, plasma, and urine before and after exercise in racehorses. We found changed patterns of metabolites in the muscle, plasma, and urine of racehorses before and after exercise.

• Archives of Pharmacal Research
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• 제23권4호
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• pp.374-380
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• 2000

Propentofylline (PPF, 3-methyl-1-(5-oxohexyl)-7-propylxanthine) has been reported to be a compound for treatment of both vascular dementia and dementia of the Alzheimer type. The short half-life (about 15 min) of PPF at the terminal elimination phase and poor bioavailability after oral administration of PPF to rabbits (Kim et al., 1992) suggest in part that this drug takes the extensive first-pass metabolism in the liver. In addition, the metabolic pathway for PPF remains unclear. The objective of this experiment is to identify urinary metabolites of PPF in rats. For the identification of the metabolites, rat urine was collected after oral administration of 100${m}g/kg$ PPF. PPF metabolite, 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine, was synthesized and confirmed by gas chromatography/mass spectroscopy (GC/MS) and $^1H$ nuclear magnetic resonance spectroscopy. The urinary metabolites of PPF were extracted with diethyl ether and identified by electron impact and chemical ionization GC/MS. One urinary metabolite was confirmed to be 3-methyl-1-(5-hydroxyhexyl)-7-propylxanthine by synthesized authentic compound. Several metabolites of monohydroxy- and dihydroxy-PPF were identified based on mass fragmentation of both intact and trimethylsilylated derivatives of PPF metabolites and the novel structure of these metabolites is suggested based on mass spectra.

• 대한물리치료과학회지
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• 제15권2호
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• pp.15-24
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• 2008

Background: The purpose of this study was to demonstrate the norepinephrine－induced nociceptive effects by monitoring catecholamines and its metabolites in human body. Methods: To exam the antisympathetic effect from the healthy volunteer(male:15, female:15) by monitoring changes of epinephrine, norepinephrine, dopamine, metanephrine, normetanephrine, and others of urine, a comparative study with warm water immersion ($40.8{\pm}0.3^{\circ}C$) and infrared (250W) was carried out. Results: The urinalysis showed that the concentration of epinephrine and norepinephrine were significantly decreased by both warm water immersion－and infrared－stimulated group of urine in 24 hours. Conclusion: Therefore, these results suggest that the diminished responsiveness on the epinephrine and norepinephrine to warm water immersion and infrared in volunteer may be, in part, related by the increased of antisympathetic effects.