Monaghan M S, Olsen K M, Ackerman B H, Fuller G L, Porter W H, Pappas A A
University of Arkansas for Medical Sciences, College of Pharmacy, Little Rock 72205.
J Toxicol Clin Toxicol. 1995;33(2):141-9. doi: 10.3109/15563659509000464.
The purpose of this investigation was to 1) compare the performance of proton nuclear magnetic resonance spectroscopy to gas chromatography head-space analysis in the measurement of serum isopropanol and its metabolite, acetone, obtained during a simulated overdose, and 2) compare pharmacokinetic parameters obtained using the two analytical techniques. Three healthy volunteers ingested 0.6 mL/kg of 70% isopropanol and blood samples were obtained at baseline, 0.16, 0.33, 0.66, 1.0, 1.5, 2.0, 3.0, 4.0, 6.0, 8.0, 12.0, and 24.0 hours post-ingestion. Resulting sera were analyzed by gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy for determination of isopropanol and acetone concentrations. A correlation between concentrations quantitated by gas chromatography head-space analysis versus proton nuclear magnetic resonance spectroscopy was determined using linear regression. Pharmacokinetic disposition parameters were determined from serum concentration-time data and compared using analysis of variance. For isopropanol, the linear regression equation which describes the relationship between gas chromatography head-space analysis and proton nuclear magnetic resonance spectroscopy was y = 1.041x - 2.180 (r2 = 0.995, p < 0.0001); for acetone, y = 1.022x - 0.946 (r2 = 0.984, p < 0.0001). Pharmacokinetic disposition parameters derived from the two analytical methods were comparable. Proton nuclear magnetic resonance spectroscopy can be used to rapidly quantitate serum isopropanol and acetone concentrations in the same sample when gas chromatography head-space analysis is unavailable. Also, proton nuclear magnetic resonance spectroscopy can be used to follow serial serum concentrations during an ingestion for the purpose of pharmacokinetic analysis.
1）比较在模拟过量摄入期间获得的血清异丙醇及其代谢产物丙酮的测量中，质子核磁共振波谱法与气相色谱顶空分析法的性能；2）比较使用这两种分析技术获得的药代动力学参数。三名健康志愿者摄入了0.6 mL/kg的70%异丙醇，并在摄入后0、0.16、0.33、0.66、1.0、1.5、2.0、3.0、4.0、6.0、8.0、12.0和24.0小时采集血样。通过气相色谱顶空分析法和质子核磁共振波谱法分析所得血清，以测定异丙醇和丙酮浓度。使用线性回归确定气相色谱顶空分析法与质子核磁共振波谱法定量的浓度之间的相关性。从血清浓度-时间数据确定药代动力学处置参数，并使用方差分析进行比较。对于异丙醇，描述气相色谱顶空分析法与质子核磁共振波谱法之间关系的线性回归方程为y = 1.041x - 2.180（r2 = 0.995，p < 0.0001）；对于丙酮，y = 1.022x - 0.946（r2 = 0.984，p < 0.0001）。两种分析方法得出的药代动力学处置参数具有可比性。当无法使用气相色谱顶空分析法时，质子核磁共振波谱法可用于快速定量同一样本中的血清异丙醇和丙酮浓度。此外，质子核磁共振波谱法可用于在摄入期间跟踪系列血清浓度，以进行药代动力学分析。
