Concentrations of diazepam and nordiazepam in 1,000 blood samples from apprehended drivers--therapeutic use or abuse of anxiolytics?
Using an in-house forensic toxicology database, we selected 1000 cases of driving under the influence of drugs (DUIDs) over a 12-month period if diazepam (D) and nordiazepam (ND) were both present in the blood samples. Quantitative analysis of D and ND in blood was done by solvent extraction (butyl acetate) and capillary column gas chromatography (GC) with a nitrogen-phosphorous (N-P) detector. The limits of quantitation of this analytical method for D and ND in blood were 0.05 mg/L. The correlation between D and ND concentrations in blood was statistically significant (r = .58, P < .001), as expected for a parent drug and its primary metabolite. However, the frequency distributions were markedly skewed to the right with mean (median) and highest concentrations of 0.37 (0.20) and 6.1 mg/L for D and 0.39 (0.20) and 5.6 mg/L for ND. The mean (median) total concentration (D + ND) was 0.76 mg/L (0.50 mg/L), and the concentration ratios D/ND and ND/D were 1.29 (median 0.95) and 1.41 (median 1.06), respectively. In 90 cases (9%), the concentration of D in blood exceeded 0.83 mg/L, which corresponds to an upper therapeutic limit in plasma (∼1.5 mg/L), assuming a plasma/blood distribution ratio of 1.8:1.
Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden. wayne.jones@rmv.se
Alan W
AW
Jones
Anita
A
Holmgren
D001334:Automobile Driving / Q000331:legislation & jurisprudence*; D002849:Chromatography, Gas / Q000379:methods; D016208:Databases, Factual; D003975:Diazepam / Q000032:analysis / Q000097:blood*; D053593:Forensic Toxicology; D006801:Humans; D057230:Limit of Detection; D003708:Nordazepam / Q000032:analysis / Q000097:blood*; D063487:Prescription Drug Misuse / Q000009:adverse effects; D015813:Substance Abuse Detection / Q000379:methods
D003708:Nordazepam; D003975:Diazepam