Charles L. Winek

Drug and chemical blood-level data 2001

Current blood-level data are presented for drugs and chemicals of toxicologic interest. The data represent an update of previously published compilations of therapeutic, toxic and lethal blood-levels.

Accidental death by nitrous oxide inhalation

Nitrous oxide is a popular inhalation anesthetic-analgesic agent. Its euphoric action and its availability have led to its abuse. We report a case of fatal accidental asphyxia due to nitrous oxide abuse. The deceased was a hospital worker who had access to the hospital supply of nitrous oxide. His death was due to hypoxemia and asphyxiation, secondary to nitrous oxide inhalation.

The study of tricyclic antidepressants in formalin-fixed human liver and formalin solutions

The stability of amitriptyline, nortriptyline, desipramine and imipramine in formalin-fixed human liver tissue and formalin solutions was investigated. The levels of the tricyclic and its primary demethylated metabolite in the frozen liver were determined and compared with levels obtained in the formalin-fixed liver and formalin solutions in which the liver was stored. It was obvious that some methylation of the secondary amine, nortriptyline, to the corresponding tertiary amine, amitriptyline, and of desipramine to imipramine took place in the formalin environment. Nortriptyline was not detected in most cases, suggesting that it may degrade more rapidly than desipramine. There was no consistent ratio between the concentration of the drug in the frozen liver tissue versus formalin-preserved tissue or versus formalin solution. The methylation rates of the secondary amines could not be quantitated. Storage of the liver tissue in formalin at room temperature resulted in leaching of the drugs into the formalin solution. The drugs tested may be detected for up to 22 months in the formalin-fixed liver and in the formalin medium.

Plasma versus bone marrow desipramine: A comparative study

Correlation between plasma and bone marrow tricyclic antidepressants has not been studied before. Two groups of rabbits were given 10 and 20 mg of desipramine/kg body weight, respectively. Desipramine was administered to the animals once daily by mouth for 5 days. On the fifth day the animals were sacrificed and blood and bone marrow samples were collected and analyzed using a high performance liquid chromatographic (HPLC) method. Data showed that a correlation exists between bone marrow and blood desipramine. The bone marrow desipramine concentration increased as its blood levels increased. The average ratio of bone marrow to blood desipramine +/- S.D. (standard deviation) in both dosage groups was 37.2 +/- 4.46 with a range of 30.99-44.82. This investigation is promising and shows that bone marrow could be used as an alternative tissue in the absence of a suitable blood sample.

The stability of several compounds in formalin fixed tissues and formalin-blood solutions

Buffered formalin solutions were added to spiked blood samples containing diazepam, phenytoin, carbon monoxide and cyanide to give formalin-whole blood solutions of 5 and 8%. Sections of liver positive for desipramine, phenobarbital and phenytoin were placed in separate 5 and 8% formalin-water solutions. The formalin-blood solutions were monitored daily for 30 days, while the fixed liver and formalin-water samples were analyzed once a week for 4 weeks. In the formalin-blood solutions losses were found for diazepam and phenytoin over the 30-day period of at least 41% and 33%, respectively. Cyanide detection was not possible immediately after the addition of formalin and the presence of carboxyhemoglobin was difficult to detect after 1 week. In the liver, losses of phenobarbital and desipramine were greater than 60% while phenytoin showed little change. This study has revealed that the drugs examined at toxic concentrations can be detected, with variable recoveries, for up to 30 days after fixation with formalin. However, quantitative analysis for cyanide and carboxyhemoglobin may be significantly impaired in the presence of formaldehyde.

The effect of storage at various temperatures on blood alcohol concentration

There is a paucity of data available on the effect of storage on blood alcohol concentration (BAC) at elevated temperatures. Changes in serum alcohol concentration (SAC) and BAC were studied. Serum samples spiked with alcohol in the presence or absence of preservative were stored at 26.7 degrees, 32.2 degrees or 37.8 degrees C respectively. Serum alcohol concentrations were determined daily on days 1 through 14, and on days 21 and 35. Under these controlled conditions, no significant change in SAC was observed at the aforementioned temperatures. Whole blood samples submitted from outside agencies were initially analyzed (day 1), then stored for 35 days at different elevated temperatures before a second analysis. The average loss in BAC was 19.20 +/- 15.6, 9.95 +/- 5.7, and 15.60 +/- 6.9% when the samples were stored at 26.7, 32.2 and 37.8 degrees C, respectively. The alcohol loss from whole blood samples may be attributed to chemical oxidation rather than to elevated temperatures. It is, therefore, concluded that a whole blood sample obtained from a living individual and stored in a locker, glove compartment or other environment where the temperature is elevated, may lose 10-19% of its alcohol content over 35 days of storage. On the other hand, when a serum or plasma sample is exposed to the same environment, no significant change in SAC was observed. The utility of this information is significant to the forensic toxicologist. The results of this study suggest that a whole blood sample analyzed after exposure to elevated temperature may have had, originally, a higher BAC.

Acute overdose of zolpidem

Zolpidem (Ambien) is an imidazopyridine hypnotic recently introduced in the USA. We report a case of a fatal overdose of Ambien. A 68-year-old female ingested at least 30 tablets of 10 mg Ambien (300 mg). She was found dead at home. Toxicological analyses revealed blood concentration of 4.1, 19.3 and 2.3 micrograms/ml of zolpidem, meprobamate and carisoprodol, respectively.

Cyanide poisoning as a mode of suicide

Abstract A five-year survey (1970–1975) of suicides was conducted in a county of 1,800,000 population. Cyanide is readily available in various forms, lethal in minute quantities and rapidly acting. Out of 700 suicides, six employed cyanide poisoning as an active manner of death.

Determination of ethchlorvynol in body tissues and fluids after embalmment

A 54 year-old female expired at her residence. Her husband, a physician, signed a certificate stating that her death was due to cerebrovascular accident (CVA) and released her body to a funeral home, where she was embalmed. Since the deceased had a long history of medical problems and drug abuse, an autopsy was performed and no evidence of CVA was found. Toxicological analyses of body fluids and tissues revealed the presence of ethchlorvynol in high concentration in the bile (112 mg/l). The bloody fluid collected from the heart contained a concentration of ethchlorvynol below the limit for quantitation. Other findings included phenobarbital (32.8 mg/l) in heart bloody fluid and methanol (an ingredient of embalming fluid). The significance of the findings is discussed in relation to embalmment prior to autopsy and toxicological analyses. Ethchlorvynol concentration in the bile is compared to other fatal cases due to ethchlorvynol overdose.

Amoxapine fatalities: Three case studies

Amoxapine (Asendin), a recently introduced dibenzoxazepine, has been effective in clinical studies for the treatment of various types of depression. Three amoxapine-related deaths are reported. Quantitation of amoxapine was carried out by gas chromatography using 3% OV-17 column. Blood amoxapine concentrations were 11.5 mg/l, 2.8 mg/l, and 0.89 mg/l. The concentrations are many-fold higher than the reported therapeutic serum concentrations of 0.21 mg/l. These cases illustrate the potential toxicity and lethality of amoxapine overdose and the need for caution in prescribing a large amount of amoxapine to patients with suicidal tendencies.