Concentrations of Diazepam and Nordiazepam in 1000 Blood Samples From Apprehended Drivers—Therapeutic Use or Abuse of Anxiolytics?

Abstract

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.

Prevalence of alcohol and other drugs and the concentrations in blood of drivers killed in road traffic crashes in Sweden

“…However, an on-going study found that only 26% of drivers with diazepam in blood had a prescription issued to them for this medication, so 84% of drivers had obtained the drug illegally (Tjäderborn, personal communication). According to the present study, the median concentration of diazepam in blood of fatally injured drivers was 0.10 mg/L, which is sub-therapeutic and much lower than the median concentration of 0.2 mg/L in apprehended drivers not involved in fatal crashes [28].…”

Rapid Characterization of Undeclared Pharmaceuticals in Herbal Preparations by Ambient Ionization Mass Spectrometry for Emergency Care

“…The results indicated that lower detection limits were achieved by TD-ESI/MS/MS than those of TD-ESI/MS for the detection of adulterant standards prepared in methanol and of those spiked in different herbal preparations (Table ). Human serum >20 μg/mL acetaminophen, >15 μg/mL caffeine, > 1.5 μg/mL diazepam, > 20 μg/mL phenytoin, and >45 μg/mL phenylbutazone . Such overdose levels encountered in actual clinical practice are far higher than the LODs of TD-ESI/MS described in this study.…”

Activation of GABA(A) receptors inhibits T cell proliferation

“…Certainly, therapeutic concentrations of diazepam may be exceeded in blood of the persons abusing it. To our knowledge, the maximum concentration of diazepam was observed in humans to be as high a 7.6 mg/L corresponding to 26.7 μM [ 43 ]. Therefore, although at standard therapeutic dosages diazepam would not affect immune cells in humans, at higher doses found in plasma of substance abusers immunological effects might take place.…”