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Venlafaxine (V) is a second-generation antidepressant approved for use in the United States in 1993. It is a derivative of phenethylamine and is structurally unrelated to first- and other second-generation antidepressants. Nevertheless, its mechanism of action is similar to other antidepressants; it inhibits the reuptake of presynaptic norepinephrine and serotonin. Its major routes of elimination involve O and N demethylation. O-Desmethylvenlafaxine (ODV) is biologically active. Therapeutic concentrations of V and ODV are approximately 0.2 and 0.4 mg/L, respectively. Three cases of drug intoxication involving V are presented. V and ODV were identified by gas chromatography-nitrogen-phosphorus detection after alkaline extraction of the biological specimen. On an HP-5 column, V and ODV elute after bupropion and fluoxetine, but prior to the first-generation antidepressants, sertraline, amoxapine, and trazodone. V and ODV were confirmed by full scan electron impact gas chromatography-mass spectrometry. The heart-blood V and ODV concentrations (mg/L) in the three cases were 6.6 and 31; 84 and 15; and 44 and 50, respectively. In Case 1, acetaminophen and diphenhydramine were found in the heart blood at 140 and 2.6 mg/L respectively. In Case 2, amitriptyline, nortriptyline, and chlordiazepoxide were found in the blood at 2.8, 0.5 and 3.3 mg/L, respectively. In each case, the manner of death was suicide.

A simple and sensitive method for determining urinary cyclohexanol, the main metabolite of cyclohexanone, by hydrolysis and gas chromatography (GC) with a flame ionization detector was developed. A 2-mL urine sample was hydrolyzed with 0.4 mL of concentrated HCl and followed by extracting twice with diethylether. Two microL of the filtrate was injected into the GC with a methyl silicone column. The detection limit is estimated to be 0.4 mg/L. The coefficient of variation for the procedure is 8% and 10% for the range of concentration 5 and 50 mg/L, respectively. The within-run variation was 5.4% and between-day variation was 9.67%. The method was verified with urine samples collected from workers exposed to cyclohexanone. An excellent correlation (r = 0.88) was observed between environmental cyclohexanone exposure and cyclohexanol in urine. The procedure is relatively simple and reproducible and it can be applied for occupational health measurement of cyclohexanone exposure.

Using gas chromatography-mass spectrometry, we investigated the urinary excretion of organic acids of 278 newborn babies in a special care unit to obtain reference data and monitor metabolism. In 101 of 584 urine samples analyzed, we found isomers of cyclohexanediol. trans-1,2-Cyclohexanediol was always most abundant, with small amounts of 1,3- and 1,4-cyclohexanediol and, sometimes, traces of cis-1,2-cyclohexanediol. Glucuronide conjugates were not detected. The probable source was the solvent cyclohexanone, which was found as a contaminant of intravenous dextrose and the parenteral feeding solution, and was also leached into the infusion fluids from the administration set. We recovered 0.89 mg (range 0.74-0.98 mg, n = 5) of cyclohexanone from 150 mL of dextrose pumped through the infusion apparatus over 24 h, the normal rate for a 1-kg premature baby. Although this is well below toxic doses reported for mature animals, more data are needed for the newborn, particularly preterm infants who have a decreased capacity for glucuronide conjugation.