• Archives of Pharmacal Research
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• 제14권2호
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• pp.130-136
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• 1991

Nicotine (100 .mu. M) was incubated with microsomes (1 mg/ml) prepared from New Zealand White rabbits. On the basis of microsomal weight, the rate of nicotine oxidation were calculated on the basis of cytochrome P-450 concentration, the specific activity of the metabolic oxidation catalyzed by lung was approximately 4 times greater than liver (6.4 vs 1, 65 nmoles nicotine oxidized. nmole cytochrome $P-450^{-1}\;min{-1})$. These studies employed several methods of altering activities of specific isozymes present in pulmonary microsomes, including the use of the isozyme2 and 6 specific inhibitor $\alpha$-methylbenzyl ABT, metabolite inhibitors, norbenzphetamine and N-hydroxyamphetamine. TCDD induction and Arochlor 1260 pretreatment. These results support the conclusion that nicotine metabolism by rabbit lung microsomes is mediated primarily by cytochrome P-450 isozyme 2.

• 분석과학
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• 제31권4호
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• pp.161-170
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• 2018

메스암페타민(methamphetamine, MA)과 암페타민(amphetamine, AP)은 전세계적으로 널리 퍼진합성 흥분제로 보건 및 사회 문제, 경제적 비용 발생 등의 다양한 문제를 일으킨다. 또한 이러한 마약은 중독 및 남용 가능성이 매우 높기 때문에 확산 방지를 위한 방안의 하나로 복용자의 생체시료에서 이들 마약을 검출하기 위한 분석법 개발이 필요하다. 따라서 본 연구에서는 액체크로마토그래피-질량분석법(liquid chromatography-tandem mass spectrometry, LC-MS/MS)를 이용하여 소변에서 MA와 4-하이드록시메스암페타민(4-hydroxymethamphetamine, 4HMA), AP, 4-하이드록시암페타민(4-hydroxyamphetamine, 4HA)을 동시에 분석할 수 있는 분석법을 개발하였고 유효성 평가를 수행하였다. 전처리 시간 단축을 위해 50000 g에서 3 min 동안 초고속원심분리 후 시료 희석 주입법을 이용하여 LC-MS/MS에 주입하였다. 분리관은 역상 C18 컬럼을 사용하였고, 정량분석을 위해 MRM (multiple reaction monitoring) 모드를 적용하였다. 가중계수 $1/x^2$에서 정량 범위는 MA는 10-2500 ng/mL, AP는 1.0-800 ng/mL, 4HA와 4HMA는 2.0-200 ng/mL로 설정하였고, 검량선의 직선성은 결정계수($r^2$)를 구하여 평가하였다. 초고속원심분리법의 효율성을 확인하기 위해 전처리 과정으로 시린지 필터(membrane-filtration)를 적용한 결과와 비교하였고, 그 결과 분석물질에 따라 6-15 % 성능이 우수한 것으로 나타났다. 일내(intra-day)와 일간(inter-day) 정밀도는 6.6 % 미만이었고, 정확도는 -14.9-11.3 % 였다. 최저정량한계(LLOQ)는 2.0 ng/mL (4HA 및 4HMA), 1.0 ng/mL (AP), 10 ng/mL (MA)로 확인되었다. 선택성, 검출한계, 희석무결성, 기질효과, 효율성, 안정성을 평가한 결과 만족스러운 측정값을 얻었다. 또한 개발된 분석법을 마약 복용자의 소변에 적용하여 분석법의 유용성을 확인하였다.

• Mass Spectrometry Letters
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• 제5권4호
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• pp.104-109
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• 2014

Nonmedical use of prescription stimulants such as methylphenidate (MPH) and amphetamine (AP) by normal persons has been increased to improve cognitive functions. Due to high potential for their abuse, reliable analytical methods were required to detect these prescription stimulants in biological samples. A direct injection liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and implemented for simultaneous determination of MPH, AP and their metabolites ritalinic acid (RA) and 4-hydroxyamphetamine (HAP) in human urine. Urine sample was centrifuged and the upper layer ($100{\mu}L$) was mixed with $800{\mu}L$ of distilled water and $100{\mu}L$ of internal standards ($0.2{\mu}g/mL$ in methanol). The mixture was then directly injected into the LC-MS/MS system. The mobile phase was composed of 0.2% formic acid in distilled water (A) and acetonitrile (B). Chromatographic separation was performed by using a Capcell Pak MG-II C18 ($150mm{\times}2.0mm$ i.d., $5{\mu}m$, Shiseido) column and all analytes were eluted within 5 min. Linear least-squares regression with a 1/x weighting factor was used to generate a calibration curve and the assay was linear from 20 to 1500 ng/mL (HAP), 40-3000 ng/mL (AP and RA) and 2-150 ng/mL (MPH). The intra- and inter-day precisions were within 16.4%. The intra- and inter-day accuracies ranged from -15.6% to 10.8%. The limits of detection for all the analytes were less than 4.7 ng/mL. The suitability of the method was examined by analyzing urine samples from drug abusers.