Measurement of serum isopropanol and the acetone metabolite by proton nuclear magnetic resonance: application to pharmacokinetic evaluation in a simulated overdose model.
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.
Monaghan
M S
MS
University of Arkansas for Medical Sciences, College of Pharmacy, Little Rock 72205.
Olsen
K M
KM
Ackerman
B H
BH
Fuller
G L
GL
Porter
W H
WH
Pappas
A A
AA
D000433:1-Propanol / Q000097:blood* / Q000378:metabolism / Q000493:pharmacokinetics / Q000506:poisoning*; D000096:Acetone / Q000097:blood*; D000328:Adult; D000704:Analysis of Variance; D002849:Chromatography, Gas; D006801:Humans; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015203:Reproducibility of Results
D000096:Acetone; D000433:1-Propanol