Segmental analysis for cocaine and metabolites by HPLC in hair of suspected drug overdose cases

Hair samples of eight postmortem cases were analyzed in segments of 1 to 3 cm for cocaine, benzoylecgonine and cocaethylene. Samples were prepared for analysis by digestion in 0.1 M HCl and subsequent extraction with mixed-mode solid-phase extraction columns. Measurement was made by reversed-phase, narrow-bore HPLC and fluorescence detection using two laboratory-made internal standards. The concentrations were in the region of 0.29-316 ng/mg of hair for cocaine, 0.43-141 ng/mg of hair for benzoylecgonine and 0.93-1.83 ng/mg of hair for cocaethylene. All eight investigated cases had cocaine-positive segments. In six of the cases, all segments were positive, suggesting regular cocaine use and two showed in-between negative segments indicating an interruption or a change of the abuse intensity. The results showed a second, remarkable observation, i.e. enormous concentration differences (factor >150) for both cocaine and benzoylecgonine between the different subjects. Furthermore, interindividual cocaine/benzoylecgonine ratios ranged from 0.02 to 8.43. We believe these observations could in part be attributed to both some of the still existing limitations in the analytical approach(es), especially the mandatory hair washing steps, and in our still too limited knowledge of the hair incorporation processes. Nevertheless, in some cases, segmental analysis proved to be an important tool to distinguish, together with postmortem examination, deadly chronic abuse from single acute drug overdosage.     

Segmental analysis for cocaine and metabolites by HPLC in hair of suspected drug overdose cases

Hair samples of eight postmortem cases were analyzed in segments of 1 to 3 cm for cocaine, benzoylecgonine and cocaethylene. Samples were prepared for analysis by digestion in 0.1 M HCl and subsequent extraction with mixed-mode solid-phase extraction columns. Measurement was made by reversed-phase, narrow-bore HPLC and fluorescence detection using two laboratory-made internal standards. The concentrations were in the region of 0.29–316 ng/mg of hair for cocaine, 0.43–141 ng/mg of hair for benzoylecgonine and 0.93–1.83 ng/mg of hair for cocaethylene. All eight investigated cases had cocaine-positive segments. In six of the cases, all segments were positive, suggesting regular cocaine use and two showed in-between negative segments indicating an interruption or a change of the abuse intensity. The results showed a second, remarkable observation, i.e. enormous concentration differences (factor >150) for both cocaine and benzoylecgonine between the different subjects. Furthermore, interindividual cocaine/benzoylecgonine ratios ranged from 0.02 to 8.43. We believe these observations could in part be attributed to both some of the still existing limitations in the analytical approach(es), especially the mandatory hair washing steps, and in our still too limited knowledge of the hair incorporation processes. Nevertheless, in some cases, segmental analysis proved to be an important tool to distinguish, together with postmortem examination, deadly chronic abuse from single acute drug overdosage.     

Accidental insulin overdose

Exogenous insulin has been used for many years to treat diabetes mellitus. Due to the complex nature of insulin therapy, there have been numerous accidental overdoses by these patients. Unfortunately, in other instances, insulin has been used as an agent for suicide and homicide in diabetics as well as nondiabetics. Presented here is a fatal case of accidental insulin overdose in a nondiabetic. Following the case presentation, we review insulin pharmacology and the methods of diagnosing insulin overdose postmortem. In any case of insulin overdose, a comprehensive scene investigation to document the amount and type of insulin used, along with information revealing the source of the insulin is critical. In addition, a complete autopsy, including appropriate laboratory studies, is needed to make a diagnosis in these cases. Proper attention should be given to collection and storage of blood samples, as these specimens often yield the strongest evidence of insulin overdose.     

Suicide by gabapentin overdose

Gabapentin is an antiepileptic drug that is prescribed for both FDA-approved and multiple off-label conditions, and has a relatively safe side-effect profile. Rare cases of overdose-related adverse effects have been reported in the literature. Described herein are the circumstances and autopsy findings of a 62-year-old woman with a history of depression, whose death was caused by intentional ingestion of excess gabapentin. The postmortem peripheral blood gabapentin concentration as determined by high-performance liquid chromatography/tandem mass spectroscopy was 88 μg/mL. Previously reported cases of individuals surviving gabapentin overdoses are discussed and compared with this case. Based on a review of the available literature, this appears to be the first published report of a death due solely to gabapentin toxicity.     

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 μg/ml of zolpidem, meprobamate and carisoprodol, respectively.     

A fatal dothiepin overdose

High pressure liquid chromatography coupled to photodiode array detector and capillary gas chromatography coupled to mass spectrometry were employed to quantify dothiepin in biological fluids, tissues and hair in a death attributed to oral dothiepin (Prothiaden^R) ingestion. The blood concentration of dothiepin was 5.75 mg/l. Hair analysis clearly indicated a chronic antidepressant exposure, with a dothiepin concentration of 1.89 ng/mg hair. Results are discussed in the light of the existing literature.     

Timely antemortem and postmortem concentrations in a fatal carbamazepine overdose.

There are no published reports that include both timely antemortem and postmortem carbamazepine concentrations after massive overdose. We report a fatal overdose of carbamazepine with both timely antemortem and postmortem carbamazepine concentrations. Carbamazepine concentrations were 47.7 mcg/mL 2 h antemortem and 53 mcg/mL at 9 h postmortem. The slight rise in drug concentration may reflect continued absorption of the drug in the last 2 h before death. Postmortem carbamazepine concentrations drawn from a peripheral vessel in this patient appeared to reflect drug concentrations at the time of death.     

Fatal outcome of Ecstasy overdose

Consumption of amphetamine derivatives has considerably increased in Germany since the early nineties. Again and again intoxications with lethal outcome have also been reported, especially after physical activities such as intensive dancing. The authors present a case of an obviously suicidal intoxication of a 21-year-old man who was found dead with marked cuts on the right forearm. Toxicological tests showed in particular 3, 4-methylene-dioxymethamphetamine (MDMA). The results of the hair analysis revealed chronic consumption, but no cellular liver damage could be demonstrated. When examining the body fluids and organs, the highest concentrations by far were measured in the lungs (36.6 mg/kg), the liver (29.7 mg/kg) and the brain (29.1 mg/kg). The concentration in heart blood amounted to 10.8 mg/kg and was thus markedly higher than in peripheral blood (7.2 mg/kg). In the muscles concentrations ranged between 14.3 mg/kg and 20.2 mg/kg. On the basis of these concentrations and the available pharmacokinetic data the amount of MDMA probably consumed is assessed. It is demonstrated that for this assessment the concentrations in the muscular system are of special importance, as redistribution of highly lipophilic substances from the surrounding tissue is possible also in peripheral blood.     

Bile analysis in heroin overdose

Abstract:  Following its metabolism in the liver, morphine and its metabolites can be directly eliminated in bile. Then, they undergo the enterohepatic cycle (EHC) and mostly reappear in the circulation. We report a case showing the presence of morphine in bile (21.3 μg/mL) and hair (4.8 ng/mg) but not in blood, urine or the liver of an addict who survived in hospital for about 144 h (6 days). These data would indicate that the EHC does not play any role about 144 h after the last injection, and directly confirms that gall bladder is a storage depot for morphine. They constitute the first report of a demonstration of the effect of the EHC on morphine bioavailability in an addict, and could be considered as indication, without supporting circumstantial evidence, that the morphine level in bile is related to chronic opiate use.     

Death scene gas analysis in suspected methane asphyxia.

Two cases of methane asphyxia occurring in two boys (age 11 and 12 years) who were found at the bottom of a 37-ft (11.1-m)-deep sewer shaft are described. Attempted resuscitation of the first patient was unsuccessful and achieved only temporary stabilization of the second, who died 48 h after his discovery. Autopsies revealed relatively minor multifocal traumatic injuries, with evidence of hypoxic-ischemic encephalopathy in the patient who survived for 2 days. Subsequent analysis of gas in the shaft revealed 21% oxygen at the surface, 14.3% at a depth of 5 ft (1.5 m), and only 4.8% at depths of 10 ft (3 m) and below. Other gases detected at the lower levels were methane, nitrogen, and carbon dioxide (4.3%). These cases demonstrate the value of atmospheric gas analysis in cases of possible methane asphyxia in confirming the presence of methane and in demonstrating levels of oxygen below that necessary to support life.     

Role of alcohol in heroin overdose

The relationship between ethanol and risk of heroin overdosage was studied. Statistical processing of the results of forensic chemical analysis (460 expert evaluations) carried out in Chelyabinsk Regional Bureau of Forensic Medical Expert Evaluations in 2000 was carried out. The results of morphine and ethanol measurements in the blood and urine from corpses where deaths ensued from narcotic or ethanol poisoning, were analyzed. The concentrations of morphine in the blood and urine were measured on a gaseous chromatographer with mass-selective detector (Hewlett Packard HP 6890/HP-5972). Methods for measuring urinary and blood morphine are described. The results of statistical analysis demonstrated relationships between the age and ethanol concentrations in the blood and urine; blood ethanol and total urinary and blood morphine concentrations; blood concentration of free morphine and presence of 6-monoacetylmorphine in the blood. The authors conclude that the presence of ethanol in the blood together with morphine drastically augments the risk of rapid death from respiration arrest. It can also lead to a relatively high risk of overdosage in experienced narcomaniacs using heroin and ethanol.     

Bladder rupture after intentional medication overdose

We report the case of a 51-year-old woman who had a medical history of diabetes, depression with past suicide attempts, and suicidal ideation. She was found unresponsive in a motel with multiple bottles of medicines (melatonin, carisoprodol, ativan, and clonazepam) and an unopened bottle of wine. She was transported to the local hospital and treated for benzodiazepine toxicity and aspiration pneumonitis.The decedent gradually became more alert and was extubated 3 days after hospital admission. The decedent was reportedly getting up to use the restroom when she became tachypneic and diaphoretic and complained of generalized body pain. Her condition quickly declined, and she was pronounced deceased. A postmortem examination revealed an acute bladder rupture and soft tissue hemorrhage.A review of the literature reveals that isolated bladder rupture after minimal or no trauma in association with alcohol or drug ingestion is an infrequently reported, but recognized, injury. The diagnosis of bladder rupture should be considered in a patient with lower abdominal pain, even without a history of trauma. A history of voiding or bladder dysfunction should increase the suspicion for this injury. If suspected, a retrograde cystogram should be obtained promptly. Failure to consider and recognize this injury may lead to significant morbidity.     

Fatal overdose of tramadol and alprazolam

A 30-year-old woman, with history of depression, was found dead after the ingestion of an unknown quantity of Xanax (alprazolam), Tramal (tramadol) and alcohol. At the autopsy only a slight decomposition and a diffuse visceral congestion were noticed. Biological samples obtained at autopsy were analysed to detect the presence of alprazolam, tramadol and alcohol. Blood concentrations of alprazolam, alcohol and tramadol were 0.21 mg/l, 1.29 g/kg and 38.3 mg/l, respectively.     

Fatal overdose of the herbicide bentazone

A 59-year-old woman who intentionally ingested 100-200 ml Basagran was taken to the hospital with a cardiac arrest 2 days after she had consumed the herbicide. During this period she suffered vomiting, urination and diarrhoea and she was drowsy with a muddled speech. Biological samples obtained at the autopsy were analysed and presence of bentazone, alcohol and an active metabolite of citalopram were detected. Blood concentrations of bentazone, alcohol and desmethyl-citalopram were 625 mg/kg, 0.62 g/l and 0.03 mg/kg, respectively.     

A fatality caused by heparin overdose

Because of suspected pulmonary embolism 550.000 I.U. of heparin were administered instead of 55.000 I.U. of heparin within 24 h to a 62 year old patient. The man died because of cerebral hemorrhage the following day. Autopsy findings are reported and difficulties in medical expertise are discussed.