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Death due to benzhexol toxicity
Forensic Science International 71 (1995) 9-14
ELSEVIER
Forensic Sclience International
Death due to benzhexol toxicity John A.M. Gall*, Olaf H. Drummer, Anthony J. Landgren Victorian Institute of Forensic Pathology and Department of Forensic Medicine, Monash University, 57-83 Kavanagh St., South Melbourne, 3205, Victoria, Australia
Received 22 March 1994;accepted 2 July 1994
Abstract
A rare caseof death due to benzhexol toxicity is reported in a 48-year-old schizophrenic male with a resolving empyemaand underlying patchy, mild bronchopneumonia. Toxicological analysis revealed the benzhexol blood and liver concentrations to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. Other drugs were not detected. It is suggestedthat for fatalities to occur following benzhexol intoxication, secondary contributory factors, which probably further alter the patient’s conscious state, are necessary. Keywordr:
Fknzhexol; Toxicity;
Chromatography
1. Introduction Benzhexol hydrochloride (Artane; Benzhexol; Bentex; Broflex) is an antimuscarinic drug with actions similar to those of atropine. It is frequently used both in the treatment of Parkinson’s diseaseand to counteract the extrapyramidal side-effects of certain antipsychotic drugs. Side-effectsof benzhexol are common and include a dry mouth, gastrointestinal disturbances, dizziness and blurred vision. Less commonly, psychotic disturbances have been reported with therapeutic doses [l]. Psychoses,however, have occurred with all reported toxic doses and the manifestations have included emotional lability, confusion, suspicion, hallucinations,
disori-
entation in time and place and, importantly, fluctuating consciousness[l-5]. Death resulting from benzhexol administration is rare and only four cases have been * Corresponding author. Fax: + 61 3 682 7353. 0379-0738/95/%09.500 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0379-0738(94)01607-7
10
J.A.M. Gall et al. /Forensic Sci, hr. 71 (1995) 9-14
reported in the literature [6-91. Unfortunately, very little information was given in these reports and, in three cases,the findings were complicated by the presenceof significant levels of other drugs. We report a caseof benzhexol toxicity resulting in the death of a middle-aged male with mild-moderate respiratory compromise. 2. Case A 4%year-old male was unexpectedly found dead in the bedroom of his apartment. There were no suspicious circumstancesand a suicide note was not found. The deceasedwas a schizophrenic who was on Modecate (fluphenazine decanoate; 37.5 mg every 3 weeks) and Artane (benzhexol hydrochloride; 6 mg daily in divided doses)and was being treated in an outpatient programme. He was addicted to CocaCola and was a heavy smoker. Two weeks prior to death, he was commenced on erythromycin for a productive cough and, the week before death, was treated with Granocol granules (sterculia and frangula bark) for constipation, thought to be due to either Modecate or Artane. On his last visit to the local medical officer, his cough was improving and he was noted to be showing early signs of tardive dyskinesia. He did not have a history of either threatened suicide or attempted suicide. Within the bedroom, a partly used bottle of Artane was found in addition to partly used containers of Granocol granules, erythromycin (250 mg capsules), Bricanyl elixir (terbutaline; 300 &ml), Nystatin lozenges (100 000 units) and Ventolin Rotacaps (salbutamol; 200 pg). 3. Autopsy findings
An autopsy was performed 2 days after the body was discovered. There were no findings of note on external examination. The deceasedwas 174 cm in length and weighed 67 kg. Internally, there was a moderately large, resolving, left-sided empyema located on the infero-lateral aspect of the left lower lung lobe with a mildmoderate amount of pus and loculated areas containing a straw-coloured fluid. Approximately 300 ml of fluid was present within the left pleural cavity. The right lung weighed 674 g and the left lung 900 g. On cut section, the left lower lung was oedematous,with patchy areas of consolidation. Bilaterally, there was a mild upper lobe emphysema.The right lung and left upper lobe were otherwise unremarkable. Mucopurulent sputum was present within the trachea. Examination of the other systems revealedonly mild atheroma within the aorta and coronary, carotid and pulmonary arteries, a slightly enlarged liver (2225 g) and features of benign nephrosclerosis which were consistent with the deceased’sage. Histologically, a bilateral, patchy bronchopneumonia was present (Fig. 1A). In the left lung, there was extensive oedema. Sections from the left lower lobe pleura showed fibrin deposition on the surface with organisation and a mild suppurative acute inflammatory infiltrate (Fig. 1B). Within the midbrain, the substantia nigra was normal but there was a diffuse spongiform change between myelin fibres (Fig. 2). Specimensof cerebellum and cerebrum were not processed for histology. The liver showed a moderate steatosis.
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
II
Fig. I. (A) Section of left lower lung showing a very patchy, mild bronchopneumonia. (B) Left lower lung pleural with surface fibrin deposition, early organisation and the presence of foci of suppuration (arrow).
Microbiological analysis of the left pleural fluid revealed neutrophils and grampositive cocci, and grew a culture of mixed flora and an overgrowth of Proteus species. A left lung swab revealed numerous neutrophils and gram-positive cocci and grew Streptococcus milleri. 4. Toxicological analysis
Samples of urine, femoral artery blood, gastric contents and lung fluid were re-
Fig. 2. Midbrain
showing a diffuse spongiform change between myelin fibres
12
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
tained for a full toxicological examination. Urine was screenedfor opiates, amphetamines, cocaine metabolites, cannabinoids, barbiturates and benzodiazepinesusing an enzyme-multiplied immunoassay (EMIT). Blood was analysed for basic drugs on a capillary column gas chromatograph, using a nitrogen-phosphorous detector and butyl chloride as the extracting solvent [lo]. This system detects most neuroleptics, antidepressants, benzodiazepines, barbiturates and narcotics. In addition, gradient elution high performance liquid chromatography (HPLC), using a photodiode array detector, was used to assay for analgesics, barbiturates, non-steroidal anti-inflammatory drugs, diuretics and the chloral hydrate metabolite, trichloroethanol [l 11. Assaysfor carbon monoxide and ethyl alcohol were undertaken using standard procedures. Benzhexol was quantified by HPLC using a Spherisorb-ODS column (10 cm x 0.5 cm) and 55% acetonitrile in 10 mM potassium phosphate buffer (pH 3.0) as the mobile phase. Detection was by ultraviolet absorbance at 214 nm at a flow rate of 1.5 ml/min. Benzhexol was extracted from peripheral blood (1 ml) and liver homogenate by alkalinising with 2% tetraborate (1 ml) and 5% isoamyl alcohol in hexane (8 ml). The solvent layer was transferred to a clean glass extraction tube and extracted with 200 ~1 of 0.2% phosphoric acid (v/v). An aliquot (50 ~1) of the dilute phosphoric acid solution was injected into the HPLC system. Pentazocine was used as an internal standard, and standards of benzhexol were prepared in both drug-free blood and liver homogenate. Stomach contents were diluted with methanol and centrifuged, and an aliquot injected directly into the HPLC. Concentrations of drugs were estimated from standards of unextracted benzhexol. Using thesetechniques, significant levels of exogenous drugs other than benzhexol were not detected. Benzhexol concentrations in femoral artery blood and liver were estimated to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. 5. Discussion
Death associatedwith the use of benzhexol is a very rare occurrence. Dowling and Robins [6] reported a fatality in a 55-year-old male with suicidal intent, following the consumption of an uncertain quantity of amitriptyline and benzhexol tablets. Toxicological analysis at autopsy revealed the blood amitriptyline, benzhexol and ethanol levels to be 0.27 mg/l, 0.8 mg/l and O.lO%,respectively. Three other fatalities associatedwith benzhexol have been reported [7-91 and in thesecasesthe blood concentrations have been in the range 0.03-0.24 mgll. In one case,in which the benzhex01 level was 0.24 mg/l, there was an associated significant concentration of both diazepam and ethanol together with a postmortem finding of aspiration of vomitus [9]. On file in this Institute, which processesall toxicological analyses for coronial investigations in the State of Victoria, there are only three other cases involving benzhexol toxicity where the blood concentrations have been in the range 0.3-1.8 mg/l. In all of these cases,significant natural diseasewas not identified. However, toxic levels of other drugs were found in addition to benzhexol. A few non-fatal overdoses of benzhexol have been reported [l-5] with single doses in the range
J.A.M. Gall et al. /Forensic Sci. Int. 71 (1995) 9-14
13
42-300 mg. In all cases,severe psychosesdeveloped, usually within several hours, but there was full recovery over the ensuing days. In the current case,although a left-sided pleural empyema, a very patchy bilateral bronchopneumonia and bilateral emphysema were identified, the extent of the diseaseprocesswas not sufficiently extensive and severeto cause death in an otherwise fit male. Further, the findings were of an resolving empyema which correlated well with the clinical impression prior to death of an improving respiratory condition. Spongiform changeswere observed histologically in the central nervous system, but these features are non-specific and could be consistent with either cytotoxic oedema,hypoxia or cardiac arrest; all possible terminal events. The benzhexol blood concentration was found to be 0.12 mg/l, which is about the mid-point of the concentrations associated with fatalities [6-91. Thus, in this case, the primary cause of death was due to benzhexol toxicity with the respiratory conditions being contributory factors. In the past, the deceasedhad self-regulated his dose of benzhexol, and it is possible that on this occasion he increased the dose to counteract the developing tardive dyskinesia. This is a plausible explanation for the toxicity, as there was an absence of any indicators of suicidal intent and the contents of the bottle of benzhexol had not been completely consumed. Of the few casesof benzhexol toxicity reported, in those that have been associated with fatalities, there have been other factors contributing to the terminal outcome. Generally, these have been drugs that cause drowsiness and respiratory depression. In the non-fatal overdoses, the reports do not indicate either that significant amounts of other drugs were taken in conjunction with benzhexol, or that there was significant organic disease.It is possible, therefore, that for fatalities to occur following benzhexol intoxication at the dosesreported to date, secondary contributory factors are necessary; factors which most probably influence the patients’ conscious state. In the current case,as can be hypothesised in the other fatal cases,the secondary factor was respiratory compromise. If this hypothesis is correct, then greater caution needs to be exercised in the prescribing of this drug, particularly in those patients who may self-regulate their dosage. Benzhexol may be considered a relatively safe drug in that there have been so few fatalities associated with its toxicity. However, the possible requirement of secondary factors to causedeath could indicate that benzhexol-induced fatalities are underreported. Similarly, the contribution of drugs to unexpected death in caseswhere significant organic diseaseis found at autopsy is also probably under-reported as, in many laboratories, toxicological analysis is not routinely undertaken. References [I]
D.A. Stephens, Psychotoxic effects of benzhexol hydrochloride (Artane). Brif. J Psychiat., I13 (1967) 213-218. [2] S.P. Singh, Benzhexol hydrochloride poisoning. Br. Med. J., I (1961) 130. [3] G.F. Morgenstern, Trihexyphenidyl (Artane) intoxication due to overdosage with suicidal intent. Can. Med. Assoc. J., 87 (1962) 79-80. [4] J.V. Ananth, H.E. Lehmann and T.A. Ban, Toxic psychosis induced by benzhexol hydrochloride. Can. Med. Assoc. J., 103 (1970) 771.
14
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
[5] P.R. Bachrich, New drugs of addiction. Br. Med. J., 1 (1964) 834-835. [6] S. Dowling and A.J. Robins, A fatal case involving benzhexol and amitriptyline. Bull. ht. Assoc. Forensic Toxicol., 20 (1990) 20-22.
[7] L. Kopjak and T.A. Jennison, Artane ingestion. Bull. Inr. Assoc. Forensic Toxicol., 12 (1976) 8. [8] G. Yamarellos, G. Dimopoulos and C.H. Stamoulis, Fatal Artane and Nortrilene. Bull. Inr. Assoc. Forensic Toxicol., 13 (1977) 32-33. [9] S. Dawling and N. Ward, A fatal case involving ethanol, benzhexol and diazepam. Bull. Int. Assoc. Forensic Toxicol., 19 (1987) 28-30. [IO] O.H. Drummer, S. Horomidis, S. Kourtis, M.L. Syrjanen and P. Tippett, Capillary gas chromatographic drug screen for use in forensic toxicology. J. Anal. Tax., in press. [l I] O.H. Drummer, A. Kotsos and I.M. McIntyre, A class-independentdrug screenfor use in forensic toxicology using a photodiode array detector. J. Anal. Tox., 17 (1993) 225-229.
ELSEVIER
Forensic Sclience International
Death due to benzhexol toxicity John A.M. Gall*, Olaf H. Drummer, Anthony J. Landgren Victorian Institute of Forensic Pathology and Department of Forensic Medicine, Monash University, 57-83 Kavanagh St., South Melbourne, 3205, Victoria, Australia
Received 22 March 1994;accepted 2 July 1994
Abstract
A rare caseof death due to benzhexol toxicity is reported in a 48-year-old schizophrenic male with a resolving empyemaand underlying patchy, mild bronchopneumonia. Toxicological analysis revealed the benzhexol blood and liver concentrations to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. Other drugs were not detected. It is suggestedthat for fatalities to occur following benzhexol intoxication, secondary contributory factors, which probably further alter the patient’s conscious state, are necessary. Keywordr:
Fknzhexol; Toxicity;
Chromatography
1. Introduction Benzhexol hydrochloride (Artane; Benzhexol; Bentex; Broflex) is an antimuscarinic drug with actions similar to those of atropine. It is frequently used both in the treatment of Parkinson’s diseaseand to counteract the extrapyramidal side-effects of certain antipsychotic drugs. Side-effectsof benzhexol are common and include a dry mouth, gastrointestinal disturbances, dizziness and blurred vision. Less commonly, psychotic disturbances have been reported with therapeutic doses [l]. Psychoses,however, have occurred with all reported toxic doses and the manifestations have included emotional lability, confusion, suspicion, hallucinations,
disori-
entation in time and place and, importantly, fluctuating consciousness[l-5]. Death resulting from benzhexol administration is rare and only four cases have been * Corresponding author. Fax: + 61 3 682 7353. 0379-0738/95/%09.500 1995 Elsevier Science Ireland Ltd. All rights reserved SSDI 0379-0738(94)01607-7
10
J.A.M. Gall et al. /Forensic Sci, hr. 71 (1995) 9-14
reported in the literature [6-91. Unfortunately, very little information was given in these reports and, in three cases,the findings were complicated by the presenceof significant levels of other drugs. We report a caseof benzhexol toxicity resulting in the death of a middle-aged male with mild-moderate respiratory compromise. 2. Case A 4%year-old male was unexpectedly found dead in the bedroom of his apartment. There were no suspicious circumstancesand a suicide note was not found. The deceasedwas a schizophrenic who was on Modecate (fluphenazine decanoate; 37.5 mg every 3 weeks) and Artane (benzhexol hydrochloride; 6 mg daily in divided doses)and was being treated in an outpatient programme. He was addicted to CocaCola and was a heavy smoker. Two weeks prior to death, he was commenced on erythromycin for a productive cough and, the week before death, was treated with Granocol granules (sterculia and frangula bark) for constipation, thought to be due to either Modecate or Artane. On his last visit to the local medical officer, his cough was improving and he was noted to be showing early signs of tardive dyskinesia. He did not have a history of either threatened suicide or attempted suicide. Within the bedroom, a partly used bottle of Artane was found in addition to partly used containers of Granocol granules, erythromycin (250 mg capsules), Bricanyl elixir (terbutaline; 300 &ml), Nystatin lozenges (100 000 units) and Ventolin Rotacaps (salbutamol; 200 pg). 3. Autopsy findings
An autopsy was performed 2 days after the body was discovered. There were no findings of note on external examination. The deceasedwas 174 cm in length and weighed 67 kg. Internally, there was a moderately large, resolving, left-sided empyema located on the infero-lateral aspect of the left lower lung lobe with a mildmoderate amount of pus and loculated areas containing a straw-coloured fluid. Approximately 300 ml of fluid was present within the left pleural cavity. The right lung weighed 674 g and the left lung 900 g. On cut section, the left lower lung was oedematous,with patchy areas of consolidation. Bilaterally, there was a mild upper lobe emphysema.The right lung and left upper lobe were otherwise unremarkable. Mucopurulent sputum was present within the trachea. Examination of the other systems revealedonly mild atheroma within the aorta and coronary, carotid and pulmonary arteries, a slightly enlarged liver (2225 g) and features of benign nephrosclerosis which were consistent with the deceased’sage. Histologically, a bilateral, patchy bronchopneumonia was present (Fig. 1A). In the left lung, there was extensive oedema. Sections from the left lower lobe pleura showed fibrin deposition on the surface with organisation and a mild suppurative acute inflammatory infiltrate (Fig. 1B). Within the midbrain, the substantia nigra was normal but there was a diffuse spongiform change between myelin fibres (Fig. 2). Specimensof cerebellum and cerebrum were not processed for histology. The liver showed a moderate steatosis.
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
II
Fig. I. (A) Section of left lower lung showing a very patchy, mild bronchopneumonia. (B) Left lower lung pleural with surface fibrin deposition, early organisation and the presence of foci of suppuration (arrow).
Microbiological analysis of the left pleural fluid revealed neutrophils and grampositive cocci, and grew a culture of mixed flora and an overgrowth of Proteus species. A left lung swab revealed numerous neutrophils and gram-positive cocci and grew Streptococcus milleri. 4. Toxicological analysis
Samples of urine, femoral artery blood, gastric contents and lung fluid were re-
Fig. 2. Midbrain
showing a diffuse spongiform change between myelin fibres
12
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
tained for a full toxicological examination. Urine was screenedfor opiates, amphetamines, cocaine metabolites, cannabinoids, barbiturates and benzodiazepinesusing an enzyme-multiplied immunoassay (EMIT). Blood was analysed for basic drugs on a capillary column gas chromatograph, using a nitrogen-phosphorous detector and butyl chloride as the extracting solvent [lo]. This system detects most neuroleptics, antidepressants, benzodiazepines, barbiturates and narcotics. In addition, gradient elution high performance liquid chromatography (HPLC), using a photodiode array detector, was used to assay for analgesics, barbiturates, non-steroidal anti-inflammatory drugs, diuretics and the chloral hydrate metabolite, trichloroethanol [l 11. Assaysfor carbon monoxide and ethyl alcohol were undertaken using standard procedures. Benzhexol was quantified by HPLC using a Spherisorb-ODS column (10 cm x 0.5 cm) and 55% acetonitrile in 10 mM potassium phosphate buffer (pH 3.0) as the mobile phase. Detection was by ultraviolet absorbance at 214 nm at a flow rate of 1.5 ml/min. Benzhexol was extracted from peripheral blood (1 ml) and liver homogenate by alkalinising with 2% tetraborate (1 ml) and 5% isoamyl alcohol in hexane (8 ml). The solvent layer was transferred to a clean glass extraction tube and extracted with 200 ~1 of 0.2% phosphoric acid (v/v). An aliquot (50 ~1) of the dilute phosphoric acid solution was injected into the HPLC system. Pentazocine was used as an internal standard, and standards of benzhexol were prepared in both drug-free blood and liver homogenate. Stomach contents were diluted with methanol and centrifuged, and an aliquot injected directly into the HPLC. Concentrations of drugs were estimated from standards of unextracted benzhexol. Using thesetechniques, significant levels of exogenous drugs other than benzhexol were not detected. Benzhexol concentrations in femoral artery blood and liver were estimated to be 0.12 mg/l and 0.5 mg/kg, respectively. Gastric contents contained 0.4 mg of benzhexol. 5. Discussion
Death associatedwith the use of benzhexol is a very rare occurrence. Dowling and Robins [6] reported a fatality in a 55-year-old male with suicidal intent, following the consumption of an uncertain quantity of amitriptyline and benzhexol tablets. Toxicological analysis at autopsy revealed the blood amitriptyline, benzhexol and ethanol levels to be 0.27 mg/l, 0.8 mg/l and O.lO%,respectively. Three other fatalities associatedwith benzhexol have been reported [7-91 and in thesecasesthe blood concentrations have been in the range 0.03-0.24 mgll. In one case,in which the benzhex01 level was 0.24 mg/l, there was an associated significant concentration of both diazepam and ethanol together with a postmortem finding of aspiration of vomitus [9]. On file in this Institute, which processesall toxicological analyses for coronial investigations in the State of Victoria, there are only three other cases involving benzhexol toxicity where the blood concentrations have been in the range 0.3-1.8 mg/l. In all of these cases,significant natural diseasewas not identified. However, toxic levels of other drugs were found in addition to benzhexol. A few non-fatal overdoses of benzhexol have been reported [l-5] with single doses in the range
J.A.M. Gall et al. /Forensic Sci. Int. 71 (1995) 9-14
13
42-300 mg. In all cases,severe psychosesdeveloped, usually within several hours, but there was full recovery over the ensuing days. In the current case,although a left-sided pleural empyema, a very patchy bilateral bronchopneumonia and bilateral emphysema were identified, the extent of the diseaseprocesswas not sufficiently extensive and severeto cause death in an otherwise fit male. Further, the findings were of an resolving empyema which correlated well with the clinical impression prior to death of an improving respiratory condition. Spongiform changeswere observed histologically in the central nervous system, but these features are non-specific and could be consistent with either cytotoxic oedema,hypoxia or cardiac arrest; all possible terminal events. The benzhexol blood concentration was found to be 0.12 mg/l, which is about the mid-point of the concentrations associated with fatalities [6-91. Thus, in this case, the primary cause of death was due to benzhexol toxicity with the respiratory conditions being contributory factors. In the past, the deceasedhad self-regulated his dose of benzhexol, and it is possible that on this occasion he increased the dose to counteract the developing tardive dyskinesia. This is a plausible explanation for the toxicity, as there was an absence of any indicators of suicidal intent and the contents of the bottle of benzhexol had not been completely consumed. Of the few casesof benzhexol toxicity reported, in those that have been associated with fatalities, there have been other factors contributing to the terminal outcome. Generally, these have been drugs that cause drowsiness and respiratory depression. In the non-fatal overdoses, the reports do not indicate either that significant amounts of other drugs were taken in conjunction with benzhexol, or that there was significant organic disease.It is possible, therefore, that for fatalities to occur following benzhexol intoxication at the dosesreported to date, secondary contributory factors are necessary; factors which most probably influence the patients’ conscious state. In the current case,as can be hypothesised in the other fatal cases,the secondary factor was respiratory compromise. If this hypothesis is correct, then greater caution needs to be exercised in the prescribing of this drug, particularly in those patients who may self-regulate their dosage. Benzhexol may be considered a relatively safe drug in that there have been so few fatalities associated with its toxicity. However, the possible requirement of secondary factors to causedeath could indicate that benzhexol-induced fatalities are underreported. Similarly, the contribution of drugs to unexpected death in caseswhere significant organic diseaseis found at autopsy is also probably under-reported as, in many laboratories, toxicological analysis is not routinely undertaken. References [I]
D.A. Stephens, Psychotoxic effects of benzhexol hydrochloride (Artane). Brif. J Psychiat., I13 (1967) 213-218. [2] S.P. Singh, Benzhexol hydrochloride poisoning. Br. Med. J., I (1961) 130. [3] G.F. Morgenstern, Trihexyphenidyl (Artane) intoxication due to overdosage with suicidal intent. Can. Med. Assoc. J., 87 (1962) 79-80. [4] J.V. Ananth, H.E. Lehmann and T.A. Ban, Toxic psychosis induced by benzhexol hydrochloride. Can. Med. Assoc. J., 103 (1970) 771.
14
J.A.M. Gall et al. /Forensic Sci. ht. 71 (1995) 9-14
[5] P.R. Bachrich, New drugs of addiction. Br. Med. J., 1 (1964) 834-835. [6] S. Dowling and A.J. Robins, A fatal case involving benzhexol and amitriptyline. Bull. ht. Assoc. Forensic Toxicol., 20 (1990) 20-22.
[7] L. Kopjak and T.A. Jennison, Artane ingestion. Bull. Inr. Assoc. Forensic Toxicol., 12 (1976) 8. [8] G. Yamarellos, G. Dimopoulos and C.H. Stamoulis, Fatal Artane and Nortrilene. Bull. Inr. Assoc. Forensic Toxicol., 13 (1977) 32-33. [9] S. Dawling and N. Ward, A fatal case involving ethanol, benzhexol and diazepam. Bull. Int. Assoc. Forensic Toxicol., 19 (1987) 28-30. [IO] O.H. Drummer, S. Horomidis, S. Kourtis, M.L. Syrjanen and P. Tippett, Capillary gas chromatographic drug screen for use in forensic toxicology. J. Anal. Tax., in press. [l I] O.H. Drummer, A. Kotsos and I.M. McIntyre, A class-independentdrug screenfor use in forensic toxicology using a photodiode array detector. J. Anal. Tox., 17 (1993) 225-229.