Forensic Science, 6 (1975) 135-136 0 Elsevier Sequoia S.A., Lausanne - Printed
NITRITE
135 in the Netherlands
TEST FOR METHAQUALONE
A. B. SIDLE
Norwood
Technical
College, Tooley
Street,
London
SE1 2JR (Gt. Britain)
B. WIDDOP Poisons
Unit, Guy’s Hospital,
(Received
July
15, 1975;
London
accepted
SE1 9RT (Gt. Britain)
October
1,1975)
SUMMARY Details of a simple qualitative test suitable for detecting milligram quantities methaqualone are presented. A similar reaction undergone by 2,4,6-triaminopyrimidine suggests that the mechanism involves diazotisation of an intermediate product.
of
INTRODUCTION
Methaqualone is a non-barbiturate hypnotic drug available either as Melsedin (Boots) or in combination with diphenhydramine as Mandrax (Roussel). Over a million prescriptions are written annually in the U.K. and therefore its occurrence in accidental and suicidal poisoning is not uncommon. Various methods have been proposed for the detection of methaqualone in biological samples ranging from ultra-violet spectrophotometry [l] to thin-layer chromatography [2, 31. In addition, the forensic toxicologist may isolate milligram quantities of the drug from the liver and gastro-intestinal tract and apply infra-red spectroscopy, mass-spectroscopy and other refined analytical techniques. In these circumstances, i.e. when relatively large amounts of the compound are available, the following simple qualitative test may be helpful.
METHOD
A combustion tube (7.5 X 1 cm) containing a mixture of approximately 10 mg of methaqualone and 0.1 g of sodium nitrite is heated in a Bunsen flame whilst held in a semi-horizontal position, Within a few seconds a violet band appears a short distance further up the tube. A readily detectable positive is obtainable with methaqualone quantities of the order 2-3 mg especially if the tube is allowed to cool and the contents are shaken with a little diethyl ether to reveal a purple-pink extract. Although stable indefinitely in the solid form, a solvent extract of the product loses its colour within a few hours.
136
It would seem that reaction takes place in the vapour phase in the presence of a suitable surface, since, if the test is carried out in a boiling tube, a negative result is obtained. This can be circumvented either by preheating the side of the tube immediately prior to fusion, or by inserting a glass rod, flattened at the end, and holding this just above the mixture. Other drugs subjected to the test were: amylobarbitone, quinalbarbitone, phenobarbitone, pentobarbitone, cyclobarbitone, glutethimide, salicylic acid and amitriptyline.
DISCUSSION
Attempts to isolate the compound responsible for the violet colour have so far been unsuccessful. However, a recent publication by Nitidandhaprabhas [4] describes a similar reaction undergone by 2,4,6_triaminopyrimidine with nitrite under acid conditions. In fact this is cited as a specific reaction for the nitrite ion. It seems likely that the violet colour produced with 2,4,6_triaminopyrimidine is due to diazotisation of one or more of the amino groups. Similarly, thermal treatment of methaqualone hydrochloride in the presence of sodium nitrite may produce an intermediate compound amenable to diazotisation. Certainly, gas-liquid chromatography and infrared spectroscopy has shown that only a minor portion of the drug is converted to the violet material. Work aimed at isolating the compound and elucidating its structure continues. Finally, the colour of the vapour is distinctly reminiscent of the violet vapours of iodine. This prompts a tentative suggestion of “methaqualone violet” for the name of the coloured product.
REFERENCES 1 A. Hendrick2 and A. de Leenheer, Clinical toxicology of the metabolites of methaqualone in man, J. Eur. Toxicol., 1 (1969) 56. 2 D. Burnett, J. H. Goudie and J. Munro Sheriff, Detection of methaqualone and its metabolites in urine, J. Clin. Path., 22 (1969) 602. 3 J. T. Allen, D. Fry and V. Markes, Urine spot-test for methaqualone, Lancet, I (1970) 951. 4 0. Nitidandhaprabhas, Violet for nitrite ion, J. Chem. Educ., 52 (1975) 64.
NITRITE
135 in the Netherlands
TEST FOR METHAQUALONE
A. B. SIDLE
Norwood
Technical
College, Tooley
Street,
London
SE1 2JR (Gt. Britain)
B. WIDDOP Poisons
Unit, Guy’s Hospital,
(Received
July
15, 1975;
London
accepted
SE1 9RT (Gt. Britain)
October
1,1975)
SUMMARY Details of a simple qualitative test suitable for detecting milligram quantities methaqualone are presented. A similar reaction undergone by 2,4,6-triaminopyrimidine suggests that the mechanism involves diazotisation of an intermediate product.
of
INTRODUCTION
Methaqualone is a non-barbiturate hypnotic drug available either as Melsedin (Boots) or in combination with diphenhydramine as Mandrax (Roussel). Over a million prescriptions are written annually in the U.K. and therefore its occurrence in accidental and suicidal poisoning is not uncommon. Various methods have been proposed for the detection of methaqualone in biological samples ranging from ultra-violet spectrophotometry [l] to thin-layer chromatography [2, 31. In addition, the forensic toxicologist may isolate milligram quantities of the drug from the liver and gastro-intestinal tract and apply infra-red spectroscopy, mass-spectroscopy and other refined analytical techniques. In these circumstances, i.e. when relatively large amounts of the compound are available, the following simple qualitative test may be helpful.
METHOD
A combustion tube (7.5 X 1 cm) containing a mixture of approximately 10 mg of methaqualone and 0.1 g of sodium nitrite is heated in a Bunsen flame whilst held in a semi-horizontal position, Within a few seconds a violet band appears a short distance further up the tube. A readily detectable positive is obtainable with methaqualone quantities of the order 2-3 mg especially if the tube is allowed to cool and the contents are shaken with a little diethyl ether to reveal a purple-pink extract. Although stable indefinitely in the solid form, a solvent extract of the product loses its colour within a few hours.
136
It would seem that reaction takes place in the vapour phase in the presence of a suitable surface, since, if the test is carried out in a boiling tube, a negative result is obtained. This can be circumvented either by preheating the side of the tube immediately prior to fusion, or by inserting a glass rod, flattened at the end, and holding this just above the mixture. Other drugs subjected to the test were: amylobarbitone, quinalbarbitone, phenobarbitone, pentobarbitone, cyclobarbitone, glutethimide, salicylic acid and amitriptyline.
DISCUSSION
Attempts to isolate the compound responsible for the violet colour have so far been unsuccessful. However, a recent publication by Nitidandhaprabhas [4] describes a similar reaction undergone by 2,4,6_triaminopyrimidine with nitrite under acid conditions. In fact this is cited as a specific reaction for the nitrite ion. It seems likely that the violet colour produced with 2,4,6_triaminopyrimidine is due to diazotisation of one or more of the amino groups. Similarly, thermal treatment of methaqualone hydrochloride in the presence of sodium nitrite may produce an intermediate compound amenable to diazotisation. Certainly, gas-liquid chromatography and infrared spectroscopy has shown that only a minor portion of the drug is converted to the violet material. Work aimed at isolating the compound and elucidating its structure continues. Finally, the colour of the vapour is distinctly reminiscent of the violet vapours of iodine. This prompts a tentative suggestion of “methaqualone violet” for the name of the coloured product.
REFERENCES 1 A. Hendrick2 and A. de Leenheer, Clinical toxicology of the metabolites of methaqualone in man, J. Eur. Toxicol., 1 (1969) 56. 2 D. Burnett, J. H. Goudie and J. Munro Sheriff, Detection of methaqualone and its metabolites in urine, J. Clin. Path., 22 (1969) 602. 3 J. T. Allen, D. Fry and V. Markes, Urine spot-test for methaqualone, Lancet, I (1970) 951. 4 0. Nitidandhaprabhas, Violet for nitrite ion, J. Chem. Educ., 52 (1975) 64.
