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PubMed2002

Toxicological screening for drugs of abuse in samples adulterated with household chemicals.

OBJECTIVES: Urine samples that tested positive for two drugs of abuse, namely cannabis and methaqualone, were reassayed in the presence or absence of common household chemicals: Jik (sodium hypochlorite), Dettol (chloroxylenol), G-cide Plus (glutaraldehyde), Perle Hand Soap, ethanol, isopropanol and peroxide (20 volumes). These chemicals are frequently used for the adulteration of urine samples. SETTING: Department of Pharmacology, University of Stellenbosch. METHODS: Household chemicals, at three different concentrations, were added to urine samples that tested positive for methaqualone and cannabis. Samples were reanalysed on an ETS Plus Analyser (Syva Company, San Jose, Ca.) using Emit drugs-of-abuse urine test reagents. RESULTS: Most of the chemicals tested influenced the outcome of positive toxicological screening results for these drugs. G-cide (glutaraldehyde) and Perle Hand Soap had the largest effect (false-negative) on the methaqualone test. Dettol (chloroxylenol) and Perle Hand Soap had the largest effect on the cannabis test. Higher concentrations of the adulterant were not always an indication of the extent of modification of the test result. The addition of certain chemicals (ethanol, isopropanol and peroxide) to the urine samples tested for methaqualone interfered with the test to such an extent that it gave invalid test results.

Adult↗
PubMed2001

Co-composting of pharmaceutical wastes in soil.

AIMS: Soils at a commercial facility had become contaminated with the pharmaceutical chemical residues, Probenecid and Methaqualone, and required remediation. METHODS AND RESULTS: Soil composting was investigated as an alternative to incineration for treatment. In laboratory trials, a factorial experimental design was used to evaluate organic matter amendment type and concentration, and incubation temperature. In pilot scale trials, Probenecid was reduced from 5100 mg kg(-1) to < 10 mg kg(-1) within 20 weeks in mesophilic treatments. An 8 tonne pilot scale treatment confirmed that thermophilic composting was effective under field conditions. In the full-scale treatment, 180 tonnes of soil were composted. Initial concentrations of the major contaminants in the full-scale compost treatment were 1160 mg kg(-1) and 210 mg kg(-1), for Probenecid and Methaqualone, respectively. Probenecid concentration reached the target level of 100 mg kg(-1) in 6 weeks, and removal of Methaqualone to < 100 mg kg(-1) was achieved after 14 weeks. CONCLUSION: Co-composting was effective in reducing soil concentrations of Probenecid and Methaqualone residues to acceptable values. SIGNIFICANCE AND IMPACT OF THE STUDY: Co-composting is a technology that has application in the remediation of pharmaceutical contaminants in soil.

Australia↗
PubMed2005

Cannabis and other drug use among trauma patients in three South African cities, 1999-2001.

OBJECTIVE: To assess the extent of cannabis and other drug use among patients presenting with recent injuries at trauma units in Cape Town, Port Elizabeth and Durban from 1999 to 2001. DESIGN: Cross-sectional surveys were conducted during a 4-week period at each of the above sites in 1999, 2000 and 2001. The concept of an idealised week was used to render representative samples. OUTCOME MEASURES: Cause of injury and biological markers to assess use of cannabis, methaqualone (Mandrax), opiates, cocaine, amphetamine, and methamphetamine. RESULTS: Over half of all patients tested experienced violent injuries. Excluding opiates, across sites and over time between 33% and 62% of patients tested positive for at least one drug (N = 1565). In most cases the drugs were cannabis and/or methaqualone. While no inter-city differences were found, male patients were typically more likely to test positive for drugs in general and specific drugs such as cannabis and the cannabis/methaqualone ('white pipe') combination than female patients. Drug positivity was higher in 2001 than in the previous 2 years in Cape Town, and patients injured as a result of violence in Cape Town and Durban were more likely to test positive for drugs than patients with certain other types of injuries. CONCLUSIONS: Drug use among trauma patients has remained consistently high for each of the 3 study periods. Efforts to combat the abuse of drugs such as cannabis and methaqualone would appear to be paramount in reducing the burden of injuries on health care services. The study has raised numerous issues requiring further research.

Adult↗
PubMed1981

Use of gastric fistula rats for the study of sedative, hypnotic and antianxiety drugs.

A rat gastric fistula preparation has been developed for the ready and safe administration of water-insoluble drugs. Graded doses of five sedative hypnotics - pentobarbital, secobarbital, methaqualone, diazepam and chloral hydrate - were studied using this preparation and a behavioral scale. The effect of these drugs on respiratory rate was also studied. The rat gastric fistula preparation is a stable one which allows the execution of crossover studies lasting for several months. Valid assays were obtained in comparisons of pentobarbital, secobarbital and methaqualone using both total behavior scale scores (BSS) and depression of respiratory rate. Secobarbital was equipotent to and methaqualone one-fourth as potent as pentobarbital. The slope of the chloral hydrate BSS dose-response line was statistically significantly steeper than that of pentobarbital. The diazepam BSS dose-response line was not only significantly less steep than that of pentobarbital but a plateau was seen. Neither chloral hydrate nor diazepam produced a dose-related depression of respiratory rate. The rat gastric fistula preparation has thus proved useful in characterizing the pharmacologic profiles, dose-response relationship and relative potencies of sedative hypnotics.

Animals↗
PubMed1976

A method for bioassay of physical dependence on sedative drugs in dog.

A method for an economical bioassay of physical dependence on sedatives is presented. Dogs maintained on sodium pentobarbital (200 mg/kg/24 h i.v.) were given periodic graded reductions in maintenance dose, and subscales for measuring signs of abstinence were developed. Using these subscales the relative potencies compared with sodium pentobarbital were determined for sodium secobarbital (RP = 0.85) and methaqualone (RP = 0.14). Sodium thiopental and methaqualone were assayed and found to be equipotent (RP = 0.96) in reducing the signs of abstinence from sodium pentobarbital. The occurrence of convulsions, during periods of complete reduction of the maintenance drug, became less frequent the longer the dogs had been maintained on a constant dose of sodium pentobarbital.

Animals↗
PubMed1990

Substitution of psychoactive drugs in pentobarbital-dependent rats.

The substitution of either bromazepam, diazepam, methaqualone, mazindol, nortriptyline or bupropion for pentobarbital, in dependent rats, was assessed using a continuous drug infusion method. Male, Sprague-Dawley rats were made dependent on pentobarbital during 12 days of continuous, intraperitoneal, pentobarbital infusion. On Day 13, pentobarbital was replaced with either saline, vehicle, or one of the drugs of interest and rats were infused for 24 h. On Day 14, all rats were infused, for 24 h, with saline. Changes in both body weight and behavioral indices of withdrawal were assessed during Day 13 and 14. It was observed that bromazepam and methaqualone substituted for pentobarbital in a dose-dependent fashion. Diazepam also substituted in pentobarbital dependent rats but, inexplicably, the low dose of diazepam provided better substitution than did the higher dose. On the other hand, neither mazindol or nortriptyline substituted for pentobarbital and there was a tendency for exacerbation of the withdrawal signs. Finally, it was noted that the low dose of bupropion appeared to decrease the severity of the withdrawal symptoms. The data supports the view that the substitution of compounds for pentobarbital, in dependent rats, is limited to those compounds which, presumably, possess similar mechanisms of action in the CNS.

Animals↗
PubMed1979

Studies on biologically active halogenated compounds. 1. Synthesis and central nervous system depressant activity of 2-(fluoromethyl)-3-aryl-4(3H)-quinazolinone derivatives.

Some 2-(fluoromethyl) analogues of 2-methyl-3-aryl-4-(3H)-quinazolinones have been synthesized and screened for CNS activities. It was shown that the 2-(fluoromethyl) analogues possess in general more potent CNS depressant activities and less toxicities than their parent compounds. Of particular interest were the 2-(fluoromethyl) analogues (22, 24, and 31) of methaqualone and 6-aminomethaqualone. Compound 24 was more potent in CNS depressant activity and less toxic than methaqualone. Compound 31 exhbited potent central muscle relaxing activity and markedly reduced toxicity as compared with 6-aminomethaqualone.

Animals↗
PubMed2006

Combined cannabis/methaqualone withdrawal treated with psychotropic analgesic nitrous oxide.

This article reports the first single-blind study using psychotropic analgesic nitrous oxide (PAN) for treating acute withdrawal states following the abuse of methaqualone combined and smoked with cannabis. Smoked methaqualone combined with cannabis is called "white pipe" (WP). South Africa is the only country in the world where WP is a major form of substance abuse. This article demonstrates in 101 consecutively treated patients given placebo (100% oxygen) followed by PAN that this therapy produced a measurable therapeutic effect (more than 50% improvement) in 87 patients. This study confirms that WP is a form of substance abuse confined mainly to young adult male subjects.

Adult↗
PubMed1993

Structural and molecular modeling studies of quinazolinone anticonvulsants.

Studies of derivatives of the anticonvulsant methaqualone led to the discovery that unsaturation in the 2-substituent produced active but less toxic compounds; accordingly, 2-arylethanone derivatives have been developed. The crystal structures of five 2-arylethanone derivatives of methaqualone were determined to probe structure-activity relationships. Although these compounds display different activities, the solid-state and calculated structures are similar: each compound is observed as the neamine tautomer containing an intramolecular hydrogen bond between the ethanone and the amine N atom and the molecular conformations are the same. These studies conclude that recognition of the anticonvulsants arises from specific binding of an ortho substituent on the N(3) phenyl substituent, rather than from binding of a particular conformation or tautomeric form adopted by the compound containing an ortho substituent, and that such recognition is characteristic of a broad range of anticonvulsant drugs. Crystal data: [see text].

Animals↗
PubMed1978

Changing pattern of drugs used for self-poisoning.

In 1967-76 the annual number of admissions to a poisoning treatment centre rose from 964 to 2134. The proportion of admissions caused by taking barbiturate hypnotics and methaqualone fell considerably while that caused by taking benzodiazepines and tricyclic antidepressants increased. As a result the proportion of patients admitted unconscious fell from 23% to 15%. The declining contributions of barbiturates and methaqualone and increased importance of tricyclic antidepressants were significant in all grades of coma. The change in drugs taken, however, has not yet reduced the percentage of unconscious patients needing endotracheal intubation or assisted ventilation, and hypothermia remains as common. Only hypotension has become less frequent as antidepressants replace barbiturates as the main cause of drug-induced coma. The use of salicylates for self-poisoning is declining slowly, and paracetamol poisoning is now as common.

Acetaminophen↗
PubMed1981

[Effects of afloqualone, a centrally acting muscle relaxant, on the sleep-wakefulness cycle in cats with chronically implanted electrodes (author's transl)].

The present study was carried out to elucidate whether or whether not afloqualone has a hypnotic action because of its similarity in chemical structure to methaqualone. In the sleep-wakefulness cycles during the 8-hour observation period (9:00-17:00), afloqualone increased the percentages of resting (REST) and slow wave light sleep (SWLS) stages at a dose of 25 mg/kg (p.o.), producing a moderate muscle relaxation. Even at a dose of 50 mg/kg (p.o.) where a marked muscle relaxation was produced, afloqualone had no influence on the percentage of slow wave deep sleep (SWDS) stage, though it increased the percentages of SWLS and decreased the percentages of awake (AWK), REST and fast wave sleep (FWS) stages. On the other hand, tolperisone . HCl, chlormezanone, methaqualone and pentobarbital . Na, used as the reference drugs, all increased the percentage of SWDS stage, but either decreased or had no effect on the percentages of the other four stages at pharmacologically effective doses. From these results it was concluded that afloqualone seems to be devoid of a hypnotic action and has different effects on the sleep-wakefulness cycle than those of both the hypnotics and the other muscle relaxants used.

Animals↗
PubMed1982

Assessment of the abuse liability of buspirone in recreational sedative users.

The abuse potential of buspirone, a new dopaminergic antianxiety drug, was evaluated by assessing its subjective effects in standard (10 mg) and high (40 mg) doses. These were compared with methaqualone (300 mg), diazepam (20 mg and 10 mg), and placebo in 24 casual recreational sedative users. Addiction Research Center Inventory scales measuring euphoria, sedation, dysphoria, and abuse liability were used as dependent measures. Groups of subjects received all treatments in randomized order in six weekly 4-hour sessions. Compared to placebo, methaqualone caused elevated scores on euphoria, physical sedation, and abuse liability scales compared to placebo, while 40 mg buspirone caused increased physical sedation, increased physical and mental dysphoria, and lower abuse liability scores. Overall, buspirone at 40 mg appeared unlikely to be reinforcing to recreational illicit drug users; the 10 mg dose was not discriminable from placebo or 10 mg diazepam. Diazepam at 20 mg showed some euphoriant effect compared to placebo.

Anti-Anxiety Agents↗
PubMed1984

Ethanol, marijuana, and other drug use in 600 drivers killed in single-vehicle crashes in North Carolina, 1978-1981.

Although the use of ethanol, marijuana, and other drugs may be detrimental to driving safety, this has been established by direct epidemiological evidence only for ethanol. In this study, the incidences of detection of ethanol (and other volatile substances), delta-9-tetrahydrocannabinol (THC), barbiturates, cocaine and benzoylecgonine, opiates, and phencyclidine were determined in an inclusive population of 600 verified single-vehicle operator fatalities that occurred in North Carolina in 1978 to 1981. The incidence of detection of amphetamines and methaqualone were determined for drivers accepted for study during the first two years (n = 340) and the last year (n = 260), respectively. Blood concentrations of 11-nor-deta-9-tetrahydrocannabinol-9-carboxylic acid (9-carboxy-THC) were determined in THC positive drivers. EMIT cannabinoid assays were performed on blood specimens from all drivers accepted for study during the third year, and the feasibility of using the EMIT cannabinoid assay as a screening method for cannabinoids in forensic blood specimens was investigated. The incidence of detection of ethanol (79.3%) was far greater than the incidences determined for THC (7.8%), methaqualone (6.2%), and barbiturates (3.0%). Other drugs were detected rarely, or were not detected. Blood ethanol concentrations (BECs) were usually high; 85.5% of the drivers whose bloods contained ethanol and 67.8% of all drivers had BECs greater than or equal to 1.0 g/L. Drug concentrations were usually within or were below accepted therapeutic or active ranges. Only a small number of drivers could have been impaired by drugs, and most of them had high BECs. Multiple drug use (discounting ethanol) was comparatively rare. Ethanol was the only drug tested for that appears to have a significantly adverse effect on driving safety.

Accidents, Traffic↗
PubMed1994

Impurities, adulterants and diluents of illicit heroin. Changes during a 12-year period.

Changes in the content of impurities, adulterants and diluents are described for 383 samples of illicit heroin seized in the western part of Denmark during the 12-year period 1981 through 1992. A wide range in purity was found within each year, whereas the average purity did not vary much from one year to another. The average purity of wholesale samples (45%) was only slightly higher than the purity of retail samples (36%). The SW Asian type of heroin, containing high concentrations of noscapine, predominated from the mid-eighties. Heroin base and heroin hydrochloride each accounted for approximately half of the samples during the eighties. However, in recent years the base form has become predominant. During the early eighties caffeine and procaine were the most frequent additives next to sugars. During the middle and late eighties an increasing number of heroin samples were cut with phenobarbital and methaqualone. During the early nineties the occurrence of phenobarbital and methaqualone has decreased, whereas paracetamol in combination with caffeine has become predominant. Re-analyses of samples which had been kept in storage for several years showed that most samples had not changed after being stored in the dark for a couple of years at room temperature. However, storage for more than 5 years often resulted in decomposition, particularly in samples consisting of the SW Asian type of heroin.

Acetaminophen↗
PubMed2004

Trends in adolescent alcohol and other drug use: findings from three sentinel sites in South Africa (1997-2001).

This paper aims to provide surveillance information about the extent and consequences of alcohol and other drug (AOD) use by adolescents for three sentinel sites in South Africa (Cape Town, Durban and Gauteng province). From 1997 to 2001, data were gathered from multiple sources, including specialist treatment centres, trauma units, school students, rave party attenders, and arrestees. Since the start of surveillance, an increasing proportion of South African adolescents are using AODs. Surveys point to high levels of alcohol misuse among high school students, with alcohol being the most common substance of abuse. Cannabis is the most frequently reported illicit drug of abuse among adolescents. This is reflected in the large proportion of adolescents receiving treatment for cannabis, cannabis-positive arrestees, and cannabis-positive trauma patients. Cannabis smoked together with methaqualone is the second most common primary drug of abuse in Cape Town. Arrestee data highlights the potentially negative effect of adolescent methaqualone use. Cocaine and heroin are emerging as problem drugs of abuse among adolescents in large metropolitan centres. Ecstasy (MDMA) use occurs mainly among adolescents who attend rave parties and clubs. The study points to the need for AOD intervention programmes that target young people and the need for continued monitoring of adolescent AOD use in the future.

Adolescent↗
PubMed1982

Risk factors for Kaposi's sarcoma in homosexual men.

An investigation of 20 homosexual men with histologically confirmed Kaposi's sarcoma and 40 controls revealed significant associations between Kaposi's sarcoma and use of a number of drugs (amyl nitrite, ethyl chloride, cocaine, phencyclidine, methaqualone, and amphetamine), history of mononucleosis, and sexual activity in the year before onset of the disease. Patients with Kaposi's sarcoma also reported substantially higher rates of sexually transmitted infections than did controls. Multivariate analysis indicated independent significant associations for amyl nitrite and sexual activity and showed use of phencyclidine, methaqualone, and ethyl chloride to be non-significant. Evaluated at the median exposure for patients, the analysis yielded risk-ratio estimates of 12.3 for amyl nitrite (95% confidence limits 4.2, 35.8) and 2.0 for sexual activity (95% confidence limits 1.3, 3.1).

Adult↗
PubMedDate not supplied

Prevalence of drugs used in cases of alleged sexual assault.

In recent years, there has been an increase in the number of reports in the U.S. of the use of drugs, often in conjunction with alcohol, to commit sexual assault. A study was undertaken to assess the prevalence of drug use in sexual assault cases in which substances are suspected of being involved. Law enforcement agencies, emergency rooms, and rape crisis centers across the U.S. were offered the opportunity to submit urine samples collected from victims of alleged sexual assault, where drug use was suspected, for analysis of alcohol and drugs which may be associated with sexual assault. Each sample was tested by immunoassay for amphetamines, barbiturates, benzodiazepines, cocaine metabolite (benzoylecgonine), cannabinoids, methaqualone, opiates, phencyclidine and propoxyphene. The positive screen results were confirmed by gas chromatography-mass spectroscopy (GC-MS). In addition, each sample was tested for flunitrazepam metabolites and gamma-hydroxybutyrate (GHB) by GC-MS and for ethanol by gas chromatography-flame ionization detection (GC-FID). Over a 26-month period, 1179 samples were collected and analyzed from 49 states, Puerto Rico, and the District of Columbia. The states sending the most samples were California (183), Texas (119), Florida (61), Pennsylvania (61), New York (61), Minnesota (50), Illinois (47), Indiana (44), Michigan (40), Maryland (37), Virginia (32), and Massachusetts (31). Four-hundred sixty eight of the samples were found negative for all the substances tested; 451 were positive for ethanol, 218 for cannabinoids, 97 for benzoylecgonine, 97 for benzodiazepines, 51 for amphetamines, 48 for GHB, 25 for opiates, 17 for propoxyphene, and 12 for barbiturates. There were no samples identified as positive for phencyclidine or methaqualone. In addition, 35% of the drug-positive samples contained multiple drugs. This study indicates that, with respect to alleged sexual assault cases, the prevalence of ethanol is very high, followed by cannabinoids, cocaine, benzodiazepines, amphetamines, and GHB. Although only a couple of substances have been implicated with sexual assault, this study has shown that almost 20 different substances have been associated with this crime. This study also raises the concern of illicit and licit drug use in sexual assault cases and suggests the need to test for a range of drugs in these cases. It also highlights the need to test for GHB, which is not generally tested for in a normal toxicology screen.

Benzodiazepines↗
PubMedDate not supplied

Rapid method for screening toxic drugs in serum with liquid chromatography.

We present a method for the simultaneous analysis of a variety of commonly abused drugs (acetaminophen, theophylline, salicylate, primidone, methyprylon, phenobarbital, butabarbital, ethchlorvynol, butalbital, chlordiazepoxide, pentobarbital, amobarbital, phenytoin, glutethimide, secobarbital, flurazepam, nitrazepam, methaqualone, N-desmethyldiazepam, and diazepam) in serum or plasma. Serum proteins are precipitated with an acetonitrile solution containing hexobarbital, the internal standard. The drugs are eluted from a reversed-phase column with a mobile phase consisting of acetonitrile/phosphate buffer (pH 3.2), using a two-step linear gradient, at a flow rate of 3.0 mL/min. The eluted drugs are detected by their absorption at 210 nm; their quantities are estimated from their peak heights. A complete analysis requires no longer than 45 minutes at the optimum column temperature of 50 degree C. A sensitivity of 2 mg/L of serum is attained routinely for most of the hypnotic and analgesic drugs; while methaqualone, chlordiazepoxide, diazepam, and N-desmethyldiazepam can be detected at a concentration of 0.2 mg/L. Analytical recoveries for the twenty drugs varied from 93-112%, with good reproducibility. Of more than forty drugs tested for possible interference, desmethyldoxepin, procainamide, phenylpropanolamine, mesantoin, and phenacetin interfere with the analysis of flurazepam, acetaminophen, ethchlorvynol, and phenobarbital, respectively.

Chromatography, Liquid↗