A survey of reported synthesis of methaqualone and some positional and structural isomers.

Methaqualone (2-methyl-3-o-tolyl-4(3H)-quinazolinone) is the illicit synthetic drug of choice amongst South African drug users. Historically police and forensic investigation has proven that all methaqualone seized by the South African Police Service originates from illicit manufacturing sites both inside, and outside South Africa's borders. From a drug enforcement, and forensic point of view it is, thus, of utmost importance that the various synthetic routes available to the illicit "chemist" are fully documented and understood. This is a prerequisite for effective illicit laboratory investigation, as well as chemical and precursor monitoring. This paper gives a brief introduction to the current status with regard to methaqualone use and production in South Africa, as well as an extensive review of the synthesis of methaqualone and selected isomers reported since 1946. A table summarizing synthetic routes reported in 32 reference sources is provided.     

大麻的体内代谢物THC—COOH的分析

本文介绍了定性定量分析大麻的主要代谢物ＴＨＣ－ＣＯＯＨ的两种方法。所有试管硅烷化，尿样碱性水解。ＴＬＣ法快速、简便，适用于多份检材的同时定性分析，最低检测限为５０ｎｇ．采用衍生化、ＳＩＭ的ＧＣ／ＭＳ方法灵敏，选择性、专一性强．五氟丙酸酐衍生化方法线性范围为２０－２５０ｎｇ／ｍｌ，最低检测限１０ｎｇ／ｍｌ，变异系数为８．４％，提取回收率为５８．９％；甲基化方法线性范围１０～１００ｎｇ／ｍｌ，最低检测限５ｎｇ／ｍｌ，变异系数为５．６％，提取回收率为５３．２％．     

The isolation and identification of precursors and reaction products in the clandestine manufacture of methaqualone and mecloqualone

Abuse of the hypnotic quinazolinone is well recognized and increasing. Clandestine laboratories producing methaqualone (2-methyl-3-ortho-tolyl-4(3H) quinazolinone) and mecloqualone (2-methyl-3-ortho-chlorophenyl-4(3H) quinazolinone) have been discovered throughout the United States. These laboratories utilize one of many synthesis routes to produce the illicit quinazolinone. Frequently, the clandestine chemist has little, if any, formal education in chemistry; does not keep notes; and does not label flasks and beakers containing solutions. The forensic chemist may be asked to analyze unmarked reaction mixtures that were seized in a clandestine laboratory raid. As a result, a rapid method of isolation and identification of the precursors and products of such a mixture is presented.     

A simple, rapid 125I radioimmunoassay for the detection of barbiturates in biological fluids.

A simple, rapid radioimmunoassay employing 125-I-labeled secobarbital derivative has been developed and has been shown to be capable of detecting at the nanogram level a variety of barbiturates in urine as well as in plasma.     

A semiautomated radioimmunoassay for mass screening of drugs of abuse.

A rapid, semiautomated radioimmunoassay system for detection of morphine, barbiturates, and amphetamines is described. The assays are applicable to large drug abuse screening programs. The heart of the system is the automatic pipetting station which can accomplish 600 pipetting operations per hour. The method uses 15 to 30 mul or urine for the morphine and barbiturate assay and 100 mul for the amphetamine and combined morphine/barbiturate assays. A number of other drugs were tested for interference with the assays and the results are discussed.     

Aberrant radioimmunoassay results for cannabinoids in urine

False negative and false positive radioimmunoassay results for cannabinoids in urine are reported. Such results occur infrequently and appear to be due to non-specific binding of the radiolabel by interfering substances, possibly proteins, in the specimens. False negatives arise when these substances and the non-specifically bound radiolabel are precipitated by polyethylene glycol in the separation stage of the assay, increasing the radioactivity in the bound fraction and thus lowering the assay result. False positives occur when the interfering substances and non-specifically bound radiolabel remain in solution during the separation stage, increasing the radioactivity in the free fraction and giving an erroneously high result. False positives could also occur in assays involving solid-phase antibodies or second-antibody separations. Methanol treatment of the samples prior to analysis precipitates the interfering substances and eliminates the aberrant effect. The interfering substances have not been identified through common serum proteins and semen have been excluded. No common factor in the circumstances of the cases that can account for the results has been identified.     

Identification of fetal blood stains by radioimmunoassay of alpha 1-fetoprotein.

Radioimmunoassay of alpha 1-fetoprotein(AFP) for medico-legal identification of fetal blood stains using a commercial kit is described. The AFP content in fetal blood stains on filter paper ranged from 21--320 ng/9 mm2. The protein was detected in stains of adult blood and retroplacental blood in only negligible amounts. Aging of the blood stains did not influence the values up to 1 month. The method is simple and sensitive enough for application to medico-legal-practice.     

LabCorp v. Metabolite Laboratories: The Supreme Court listens, but declines to speak.

In the United States, a longstanding legal rule exists against patenting natural phenomena. The Supreme Court recently had an opportunity to help define the boundaries and clarify the implications of this "natural phenomenon doctrine" in Laboratory Corporation of America v. Metabolite Labs., dismissed as improvidently granted. This article argues that the natural phenomenon doctrine renders both the patent claim at issue in LabCorp, and the patents that directly or indirectly claim biological correlations between genotypes and medical phenotypes, invalid or unenforceable under U.S. patent law.     

Determination of methadone in human hair by radioimmunoassay

The concentrations of methadone in human hair were measured. The washed hair was cut in 1-mm pieces approximately, then incubated overnight at 45 degrees C with 0.1 m HCl. The extracts were alcalized by 1 m NaOH and diluted by phosphate buffer, pH 7.4. The methadone concentrations were determined by radioimmunoassay. The method is simple, rapid, and practicable for routine determination.     

Occurrence of barbiturate, benzodiazepine, meprobamate, methaqualone and phenothiazine in car occupants killed in traffic accidents in the south of Sweden

An investigation of the following psychoactive drugs: barbiturate, benzodiazepine, meprobamate, methaqualone and phenothiazine, was performed on all automobile occupants killed in accidents in southern Sweden during 1977 and 1978. Of 122 drivers and 55 passengers analysed, low concentrations of these drugs were found in nine drivers and in five passengers. Thus, 7.3% of the drivers were driving under the influence of drugs and, of these, two drivers (1.6% of all analysed drivers) were also inebriated. Twenty-three per cent of the drivers were inebriated only. According to the circumstances in the accidents and the number of drivers whose analyses proved positive, drug influence seldom seems to be the cause of fatal traffic accidents.     

测定单根毛发中吗啡含量的放射免疫方法

目的 建立测定单根毛发中吗啡含量的放免方法。方法 用卵清蛋白-琥珀酰吗啡作免疫原,免疫新西兰白兔获得高品质抗血清;HPLC纯化~(125)Ⅰ-吗啡,建立放射免疫方法,测定正常人和吸毒人员单根毛发。结果 抗体亲和常数为3.25×10~(11)L/M,放化纯度为95％,比放射性112μCi/μg;方法的灵敏度为0.01ng/ml。对5例正常人及5例戒毒所吸毒人员的单根毛发进行了检测。单根毛发长度9～24cm,重量为0.7～2.1mg,5例正常人测值为1.75±0.37ng/mg(x±s);5例吸毒人员测值为471±204ng/mg(x±s)。结论 所建方法可准确定量单根毛发中吗啡的含量。     

Comparison of Abbott fluorescence polarization immunoassay (FPIA) and Roche radioimmunoassay for the analyses of cannabinoids in urine specimens.

Abbott fluorescence polarization immunoassay (FPIA) and Roche Abuscreen radioimmunoassay (RIA) were compared qualitatively with 142 urine specimens containing 11-nor-delta-9-tetrahydrocannabinol-9-carboxylic acid. Similar qualitative results were obtained in 132 specimens. When discrepent results were observed, all negative results were within 20% of the 100 ng/mL cut-off. We concluded that FPIA and RIA give comparable results to each other.     

Development of a radioimmunoassay technique for the detection of human hemoglobin in dried bloodstains

A sensitive radioimmunoassay for the detection of human hemoglobin in dried bloodstains for the purpose of forensic science species identification has been developed. Bloodstains from 13 animal species were tested and found to be negative for human blood. A minimum volume of 0.8 microL of fresh blood is required to produce sufficient stain for successful testing. Bloodstains prepared from newborn and sickle-cell bloods were determined to be human. Bloodstains ranging in age from 1 month to 6 years which had been maintained desiccated at 20 to 25 degrees C were also successfully tested. Positive results were obtained on human bloodstains stored at 24 degrees C with relative humidity ranging from 0 to 98% for a period of 3 weeks. Absolute counts per minute (CPM) decreased with increased humidity. Human bloodstains exposed to bacterial contamination (gram positive or negative species) under humid conditions for 2 weeks also tested positive. Bacterial contamination caused a decrease in CPM, but insufficient to result in an erroneous conclusion as to species of origin. Positive results were also obtained on human bloodstains stored for 6 weeks at various temperatures ranging from -16 to 37 degrees C. No significant decreases in CPM were noted for any of the temperature conditions described.     

The sensitivity of the Bayesian HPD method to the choice of prior.

Statistical sampling error is present in every statistical calculations using DNA because all such statistics rely on a sample (database) of individuals, which is used to estimate the population frequencies of alleles. Curran et al.gave a method for estimating the sampling error of the statistics based on the region of the highest density of the Bayesian posterior (HPD). The Bayesian HPD method relies on the assumption of a prior distribution for the population allele frequencies as well as Monte Carlo simulation. In this paper we answer three pivotal questions. Firstly we address the question of how many Monte Carlo iterations are required to get sufficient accuracy in our estimates of sampling error. Secondly, we address the question of the appropriate choice of the prior distribution for the population allele frequencies. Thirdly, we demonstrate the flexibility of the Bayesian HPD over other methods.     

液相色谱-串联质谱同时分析尿液中的大麻酚类和△^9-四氢大麻酸

目的建立LC/MS-MS同时检测尿液中Δ9-四氢大麻酚(THC)、大麻酚(CBN)、大麻二酚(CBD)和大麻主要代谢物Δ9-四氢大麻酸(THC-COOH)的方法.方法屎液样本经碱水解,加入氘代四氢大麻酸Δ9-d9-THC-COOH)内标,经V(正己烷)V(乙酸乙酯)=91提取,吹干,以100μL乙腈定容,利用LC/MS-MS方法进行分析.结果THC-COOH、CBN、THC和CBD的最低检测出质量浓度为0.2、0.4、1.0和2.0ng/mL;在阳性尿液中检出THC-COOH成分,质量浓度为335.9 ng/mL.结论所建立的方法简便快速、灵敏度高、专属性强,可满足检测尿液中THC、CBN、CBD以及大麻主要代谢物THC-COOH的要求.     

Unconjugated morphine in blood by radioimmunoassay and gas chromatography/mass spectrometry

Morphine, the active metabolite of heroin, is rapidly inactivated by glucuronidation at the 3 carbon. Unconjugated (pharmacologically active) morphine was measured in postmortem blood by radioimmunoassay using an antibody-coated tube kit. The kit shows less than 0.2% cross-reactivity with codeine and morphine-glucuronide. Unconjugated morphine concentrations were confirmed by gas chromatography/mass spectrometry (GC/MS) using deuterated morphine as the internal standard. The blood was precipitated with 10% trichloroacetic acid (TCA) and concentrated hydrochloric acid (HCl), centrifuged, and decanted. The supernatant was then either diluted (unhydrolyzed) or heated to 100 degrees C, 30 min (hydrolyzed), followed by a wash with 4:1 chloroform:isopropranol. The upper aqueous layer was then saturated with sodium bicarbonate (NaHCO3) and extracted with 4:1 chloroform:isopropranol. The organic layer was evaporated, derivatized with trifluoroacetic anhydride (TFA), and analyzed by selected ion monitoring (SIM) GC/MS. Comparison of the results for unconjugated morphine by radioimmunoassay and unhydrolyzed morphine by GC/MS gave a correlation coefficient of r = 0.98, n = 100. Unconjugated morphine ranged from 0 to 100% of total morphine with a mean of 42%, n = 200, for heroin or morphine involved deaths. Review of 56 putative rapid deaths gave a mean of 68% unconjugated morphine with a range of 26 to 100%. The ratio of unconjugated to total morphine was found to be stable in postmortem blood after more than a year of storage at room temperature, within the precision of the method.     

Comparison of results for quantitative determination of morphine by radioimmunoassay, enzyme immunoassay, and spectrofluorometry.

The quantitative results (accuracy and precision) for determination of opiates by radioimmunoassay (RIA), enzyme immunoassay (EMIT), and spectrofluorometry on split samples are compared. A variety of physiological samples were studied, including random urine from a methadone maintenance clinic and postmortem urine, blood, bile, brain, and lung tissue from heroin-induced or heroin-related deaths. The opiate concentrations detected by the two immunoassay methods were in good agreement with each other in the absence of interfering substances which are believed to react with the antimorphine antibodies. The immunoassay results were in agreement within the relative standard deviation with the fluorometry results in 55% of the urine samples and 80% of the blood samples. The immunological methods are superior to fluorometry for quantitation of morphine in urine samples due to quenching interferences in fluorometry from urine. They were comparable to fluorometry for quantitation of morphine in blood samples.     

Radioreceptor assay and radioimmunoassay of triazolam in urine samples from racing greyhounds

Two complimentary assay techniques were used to determine triazolam levels in greyhound urine samples following a single oral dose. The results from the trials were statistically compared. The relative non-specificity of the benzodiazepine antibody used in radioimmunoassay caused a significant difference in teh two sets of results. This was independent of hydrolysis.