Ashraf Mozayani

Marijuana is the most widespread abused, trafficked, and consumed drug in America. Although according to federal law, the use, consumption, and distribution of marijuana are illegal, approximately two-thirds of the State Governments in the U.S. and the District of Columbia have legalized marijuana for either medical or recreational purposes. Due to the passing of new controversial marijuana legislation at the state levels of government, which started with the passing of Amendments 64 and Initiative 502, respectively, in Colorado and Washington in 2012, the federal government is faced with many challenges associated with enforcing and preventing the illegal diversion of marijuana and marijuana products. Although state legislation may be passed to legalize marijuana for particular jurisdictions, under the Controlled Substances Act (CSA), distribution and possession of marijuana is still illegal on a federal level, and marijuana is classified as a Schedule I controlled substance. Contr...

Ketamine is a rapid-acting anesthetic commonly used during surgical procedures in both animals and humans, as an experimental drug in the treatment of chronic pain, and as a probe for the study of the cause of schizophrenia. When used medically as an anesthetic it is administered as an intravenous (IV) solution, but when diverted to the illicit market it can be injected, snorted, smoked, or consumed in drinks. Ketamine produces effects similar in some respects to phencyclidine (PCP) and lysergic acid (LSD), but of shorter duration. Psychedelic effects are produced quickly by low doses of the drug, although larger doses are frequently used in an attempt to produce "near-death" experiences. Convulsions and death can be caused by higher doses, although most deaths in which ketamine is detected are the result of poly-drug use or trauma. Reports of ketamine use at rave parties attended by young adults appear to be on the rise. The effects from ketamine last from 1-5 hours, and ...

The Handbook of Drug Interactions: A Clinical and Forensic Guide, part of a series of texts published by Humana Press intended for forensic science and medicine, is well suited for individuals who plan to make testifying as an expert witness a part of their professional career. The book is primarily intended for physicians and toxicologists who work in coroners’ offices, and not pharmacists. It is not a text that one would consult to look up an interaction between 2 drugs because it primarily discusses drugs of forensic interest. Other drug interaction handbooks, such as Hanstens, are much better general references for researching drug interactions because they rate the clinical significance of the drug interaction and discuss all potential drug interactions rather than just some of them. Although some drug information centers and libraries would find this book a useful reference text, I don’t recommend it in general for every pharmacist’s book shelf. Its cost will be a limiting factor for some institutions. The book is divided into 6 parts: central nervous system drugs, cardiovascular drugs, antibiotics, nonsteroidal antiinflammatory drugs, environmental and social pharmacology, and legal aspects. It reviews the pharmacology of the agents, pharmacodynamics, pharmacokinetics, metabolism, adverse reactions, and drug interactions. The section on environmental and social pharmacology includes chapters on alcohol, tobacco and nicotine, anabolic doping agents, and food– drug interactions. It does not discuss drugs of abuse, such as cocaine and marijuana, in any great detail. The discussion on metabolism and pharmacology of the drugs is very thorough; the review of drug interactions, however, is fairly superficial. The book has well-detailed chapters on alcohol and benzodiazepines, with good explanations of how other drugs and food affect drug concentrations. Discussion of some drugs, such as cyclosporine, which involves only a half page, is insufficient. Two chapters on legal aspects of drug interactions, which outline drug interaction litigation and handling of psychotropic medications in court, focus on Prozac and criminal aspects. These chapters are written like a law textbook with references to cases, which makes for interesting reading. These 2 chapters summarize case law on medications and crime entirely. The text is well indexed so that information is easily retrievable. The figures in the book are helpful to the discussion and are of good quality. The content of the book is very good. There are, however, grammatical and spelling errors in some of the chapters, which are both distracting and point to poor editing of the manuscripts. All authors are well qualified, with most having a forensic or pathology background as part of their credentials. In summary, this book has limited use for individuals primarily because of its narrow scope. It is a useful reference for those who specialize in forensics or the law because it not only explains drug interactions, but also explains the basic pharmacology and pharmacodynamics of the drugs and other agents of forensic interest such as alcohol, nicotine, and anabolic doping agents.

This communication presents the quantitation and differential distribution of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its physiologically active metabolite 3,4-methylenedioxyamphetamine (MDA) in a fatal poisoning following insufflation of MDMA, cocaine and heroin. Animal studies have demonstrated the stereoselective pharmacokinetics and neurotoxicity of these compounds; however, enantiomeric distributions have not been reported in humans. Quantitation of MDMA and MDA enantiomer was by gas chromatography/mass spectrometry (GC/MS) following chiral derivatization with N-trifluoroacetyl-L-triproyl chloride (LTPC). The decedents' blood concentration of S(+)-MDMA was slightly less than that of R(-)-MDMA (1.3 vs. 1.6 mg/l, respectively), while the S(+)- and R(-)-MDA blood concentrations were identical (0.8 mg/l). Both primary routes of excretion, bile and urine, had greater concentrations of R(-)-MDMA than the S(+) isomer. These fluids also contained twice the concentration of S(+)-MDA than the R(-)-isomer. These data indicate that S(+)-MDMA is metabolized and eliminated faster than R(-)-MDMA. The results appear to support the findings in animals regarding stereoselective metabolism of MDMA.

The pharmacology of any xenobiotic is a complex set of processes that is frequently divided into two categories: pharmacokinetics and pharmacodynamics. These two processes encompass the various steps that the body takes to transform the drug to facilitate its excretion (pharmacokinetics) and the interactions of the drug with the body which result in the observed effects (pharmacodynamics). The study of these processes includes the determination of kinetic parameters to describe the rate of elimination of the drug from the body, binding affinities to describe the interaction of the drug with endogenous receptors, and the determination of enzymes that are instrumental in these processes.

Toxicology is the science of poisons and their effects on the human body. Toxicologists deal with those substances that may cause bodily harm if taken in ­sufficient quantity, including drugs and alcohol. Since poisons are present in all aspects of our lives, toxicologists perform their craft in a number of ­different situations, including forensic labs and medical examiner offices. The

The high prevalence of alprazolam abuse translates to an increased workload for crime laboratories in characterizing seized tablets. These tablets may originate as diverted pharmaceuticals or counterfeited mimics, so efficient analytical techniques should provide confirmatory data while minimizing destruction of evidence. We offer the first report of a validated forensic method for confirming alprazolam tablets by direct analysis in real time-time of flight (DART-TOF) mass spectrometric analysis. This technique provides rapid identification of target analytes with minimal sample preparation, allowing direct analysis in the atmospheric sample gap. Selectivity is achieved through high resolution and mass accuracy, unique ion fragments, and chlorine isotopic ratios. This method utilizes fragmentation in two separate voltage functions to observe the alprazolam pseudo molecular ion at 309.09070 using 40 V and major ion fragments of 281.07197 and 205.07657 at 120 V. These parameters allow our laboratory to confirm alprazolam tablets efficiently, without compromising quality forensic standards.

Phenelzine and pheniprazine were used as substrates for metabolic studies with Cunninghamella echinulata and Mycobacterium smegmatis. Metabolites were identified by means of gas-liquid chromatography and mass spectrometry. 1-Acetyl-2-(2-phenylethyl)-hydrazine and 1-acetyl-2-(1-methyl-2-phenylethyl)hydrazine were the major products of C. echinulata metabolism of phenelzine and pheniprazine, respectively. In addition, M. smegmatis produced a second metabolite from each substrate; these metabolites were unequivocally identified as N-acetylphenylethylamine and N-acetylamphetamine from phenelzine and pheniprazine, respectively.

Synthetic cannabinoids were originally developed by academic and pharmaceutical laboratories with the hope of providing therapeutic relief from the pain of inflammatory and degenerative diseases. However, recreational drug enthusiasts have flushed the market with new strains of these potent drugs that evade detection yet endanger public health and safety. While many of these drug derivatives were published in the medical literature, others were merely patented without further characterization. AB-FUBINACA is an example of one of the new indazole- carboxamide synthetic cannabinoids introduced in the past year. Even though AB- FUBINACA has become increasingly prominent in forensic drug and toxicology specimens analyses, little is known about the pharmacology of this substance. To study its metabolic fate, we utilized Wistar rats to study the oxidative products of AB- FUBINACA in urine and its effect on gene expressions in liver and heart. Rats were injected with 5 mg/kg of AB-FUBINACA...

Acyl derivatives of phenelzine were required for pharmacological evaluation. Eight mono- and di-acyl derivatives were synthesized and characterized by gas chromatography, mass spectrometry, nuclear magnetic resonance and infrared spectrophotometry. Selective acylation was observed with both acetic anhydride and ethyl chloroformate. In aqueous medium, monoacylation yielded N1-acetyl- and N1-(ethoxy-carbonyl)-phenelzine exclusively, whereas in non-aqueous medium only N2-acetyl and N2-(ethoxycarbonyl) products were obtained. NMR temperature studies were conducted to ascertain the presence of rotational isomers and their ratios. At room temperature, one ethoxy-carbonyl and four phenelzine acetate derivatives were present as mixtures of rotamers. Preliminary evaluations of the MAO-inhibiting properties of acylated phenelzines indicate that a hydrogen atom on the N1-position of phenelzine and its derivatives is essential for activity.

Expert witnesses and others involved in toxicology are frequently asked to perform retrograde extrapolation of blood alcohol concentration (BAC) or to estimate BAC based on a proposed drinking scenario. Although many individuals are reluctant to perform these calculations and some jurisdictions expressly prohibit them, a significant number of practitioners routinely estimate BAC based on this type of calculation, using as a basis the fundamental work of Widmark. Although improvements to the Widmark formula and other data pertaining to the pharmacology of alcohol have been published, these improvements are frequently ignored when estimating BAC. This article summarizes five published models for the estimation of BAC and proposes a sixth model that incorporates recent data on the rate of absorption of alcohol from the GI tract into the existing five models. The five improved models can be computerized and used to construct comparative snapshots of the BACs calculated by the different ...

Ethanol analysis is the most commonly carried out drug testing in a forensic toxicology laboratory. Determination of blood alcohol concentration (BAC) is needed in a multitude of situations, including in postmortem analysis, driving under the influence (DUI) and drug-facilitated sexual assault (DFSA) cases, workplace drug monitoring, and probation investigations. These analyses are carried out by direct measurement of ethanol concentrations as well as of metabolic by-products, such as ethyl glucuronide (EtG) and ethyl sulfate (EtS). This review article will discuss pharmacokinetics, including absorption, distribution, and elimination of ethanol, methods for the detection of ethanol, the effect of ethanol on human performance, the role of alcohol in injuries and fatalities, and information regarding the interactions that may occur between alcohol and other drugs. Finally, an explanation will be given on how to interpret alcohol levels as well as the extrapolation and calculation of b...

A quantitative electron-capture gas chromatographic assay procedure was developed for the analysis of monoalkylhydrazines in biological samples. Application to the analysis of phenelzine was demonstrated. Four monoalkylhydrazines were analyzed in whole blood by reaction with pentafluorobenzaldehyde to form stable hydrazone derivatives which were extracted and subsequently reacted with pentafluoropropionic anhydride to give products which were very sensitive to electron-capture detection when analyzed by gas chromatography. Methylhydrazine, benzylhydrazine, phenelzine and pheniprazine each yielded single derivatives with this procedure suggesting that the analytical procedure has a broad application to the analysis of other monoalkylated hydrazines. The method was applied to monitor whole blood levels of phenelzine in rats treated intravenously with phenelzine sulphate.

1-Acetyl-2-(2-phenylethyl)hydrazine (N2-acetylphenelzine) is identified as an acetylated metabolite of phenelzine in the rat. One hour after intraperitoneal administration of a high dose of phenelzine sulfate to rats, the blood and brain of the animals were extracted and analyzed by combined gas chromatography/electron impact mass spectrometry in the total ion and selected ion modes. This procedure provided unequivocal proof of the presence of N2-acetylphenelzine in these tissues. The other possible monoacetylated metabolite of phenelzine, 1-acetyl-1-(2-phenylethyl)hydrazine (N1-acetylphenelzine), and the diacetylated derivative, 1,2-diacetyl-2-(2-phenylethyl)hydrazine, were sought, but were not detected.

Although N2-acetylphenelzine (N2AcPLZ) appears to be only a minor metabolite of phenelzine (PLZ), other investigations have demonstrated that it may be worthy of study as an antidepressant in its own right. In the present report, the possibility of ring hydroxylation as a metabolic route for PLZ was investigated in the rat. Indirect evidence for such a route was obtained using iprindole, a drug known to block ring hydroxylation. Treatment of rats with iprindole followed by PLZ was demonstrated to result in increased brain levels of PLZ and beta-phenylethylamine (control rats were treated with vehicle and then PLZ). The possibility that hydroxylation in the para-position might be a metabolic route for PLZ has led to interest in the possible use of analogues in which this position is blocked with a substituent. In preliminary acute studies at a dose of 0.1 mmol/kg p-chloro-PLZ was found to have a similar effect to PLZ on the inhibition of MAO and to lead to an elevation of catecholami...

Phenelzine and pheniprazine were used as substrates for metabolic studies with Cunninghamella echinulata and Mycobacterium smegmatis. Metabolites were identified by means of gas-liquid chromatography and mass spectrometry. 1-Acetyl-2-(2-phenylethyl)-hydrazine and 1-acetyl-2-(1-methyl-2-phenylethyl)hydrazine were the major products of C. echinulata metabolism of phenelzine and pheniprazine, respectively. In addition, M. smegmatis produced a second metabolite from each substrate; these metabolites were unequivocally identified as N-acetylphenylethylamine and N-acetylamphetamine from phenelzine and pheniprazine, respectively.

We have determined drug/metabolite concentrations and ratios of methadone (METH) to two of its metabolites (EDDP, 2-ethylidene-1, 5-dimethyl-3, 3-diphenylpyrrolidine; and EMDP, 2-ethyl-5-methyl-3,3-diphenylpyrroline) in postmortem peripheral blood and liver tissue by liquid chromatography/tandem mass spectrometry. The assays employed deuterated internal standards and multiple reaction monitoring (MRM) techniques. The assay linear range was 0.01-2.0 mg/l for each analyte. METH, EDDP, and EMDP were determined in liver and peripheral blood from 46 methadone-positive cases. METH and EDDP were detected in all specimens, whether blood or liver. EMDP was detected, only in liver, and only 17 cases, at concentrations much lower than those of EDDP. Concentrations of METH and EDDP in blood and liver from EMDP-positive cases were in ranges higher than, but overlapping with, concentrations in blood and liver from EMDP-negative cases. These data suggest that although METH is readily demethylated and cyclized to EDDP, in vivo, conversion to EMDP may be less efficient and its accumulation in postmortem tissues may be highly individual.

MK-801 (dizocilpine) is a non-competitive antagonist at the N-methyl-D-aspartate (NMDA) family of glutamate receptors in the central nervous system. It is an anticonvulsant and also shares several pharmacological properties with phencyclidine and ketamine. It is not observed routinely as a substance of abuse. The deceased, a 45-year-old white male, obtained MK-801 surreptitiously in an attempt to treat a self-diagnosed depression. He was discovered the next morning, unresponsive on the bathroom floor. An empty bottle, labeled to contain 25mg of MK-801, was found near the body. The autopsy was performed at the Joseph A Jachimczyk Forensic Center, Houston, TX. Body weight at autopsy was 88kg. Lungs were edematous and congested (right: 775g; left 700g). The heart had proportionate chambers and was otherwise unremarkable. The kidneys (right: 220g; left 225g) were smooth surfaced. The brain (1550g) was congested and without trauma. Microscopic evaluation of the heart, kidneys and lungs showed normal histology and confirmed pulmonary congestion and edema. Samples of heart blood, liver, bile, vitreous humor, stomach contents and urine were collected at autopsy. There were 550ml of stomach contents. Drugs in blood were screened by EMIT II Plus immunoassay procedures and by gas chromatography/mass spectrometry (GC/MS) of an organic solvent extract of basified blood. Alcohol was determined by gas chromatography with headspace injection. MK-801, benzodiazepines and alcohol were detected in blood. Amounts of MK-801 present in blood, bile, liver, vitreous humor and urine were 0.15, 0.29, 0.92, less than 0.1 and 0.36 mg/l (kg), respectively. The cause of death was benzodiazepine, dizocilpine and ethanol toxicity and the manner accidental.