Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism.
Evaluation of isotope ratio (IR) mass spectrometry for the study of drug metabolism.
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同位素比 (IR) 质谱法在药物代谢研究中的评价。
DOI：
10.1002/bms.1200120911
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Kaplan,IR
中科院分区：
文献类型：
--
作者：
Nakagawa,A;Kitagawa,A;Asami,M;Nakamura,K;Schoeller,DA;Slater,R;Minagawa,M;Kaplan,IR
采用13 C，15 N2标记的安替比林（AP）作为受试药物，评价了同位素比（IR）质谱法用于药物代谢和平衡研究。大鼠腹腔注射40 mg kg−1（13 C，15 N2）AP。采集呼吸、尿液、粪便和血液。除呼气外，样品在密封石英管中燃烧。通过IR质谱法分析所得CO2和N2相对于给药前样品的过量13 C和15 N。此外，分别通过气相色谱/质谱/选择离子监测（GC/MS/SIM）和高效液相色谱（HPLC）测定AP的血液水平和尿AP代谢物的累积排泄。血液中过量的13 C和15 N水平与观察到的AP水平相当，尿中13 C的回收率（42%）与HPLC数据计算的结果（45%）吻合良好。N-去甲基化是AP代谢的重要途径之一，通过呼吸中过量的13 CO2排泄（8%）最快确定。IR质谱分析补充了气相色谱/质谱和HPLC分析，并且不太复杂。
Isotope ratio (IR) mass spectrometry was evaluated for the study of drug metabolism and balance using13C,15N2‐ labelled antipyrine (AP) as a test drug. Rats were given 40 mg kg−1(13C,15N2)AP intraperitoneally. Breath, urine, faeces and blood were collected. Except for breath, samples were combusted in sealed quartz tubes. The resulting CO2and N2were analysed for excess13C and15N, relative to pre‐dose samples, by IR mass spectrometry. In addition, blood levels of AP and cumulative excretion of urinary AP metabolites were determined by gas chromatography/mass spectrometry/selected ion monitoring (GC/MS/SIM) and high‐performance liquid chromatography (HPLC) respectively. Excess13C and15N levels in blood were comparable with observed levels of AP, and urinary recoveries of13C (42%) were in good agreement with those calculated from HPLC data (45%). N‐Demethylation, one of the important pathways of AP metabolism, was most rapidly determined by excess13CO2excretion in breath (8%). The IR mass spectral analysis complemented gas chromatographic/mass spectrum and HPLC analyses, and was less complex.