Toxicology Commons^™

The Method Development And Validation Of Designer Benzodiazepines In Oral Fluid Using Solid Phase Extraction And Lc-Ms/Ms, Jenna L. Monsell

Student Theses

Oral fluid is a useful biological matrix. Collection is non-invasive, quick, observable, and its correlation between oral fluid and blood drug concentration make oral fluid an important matrix to use as a roadside test. Designer benzodiazepines have become increasingly popular over the years, adversely affecting motor skills and leading to driving under the influence. Many previous studies have focused on the method development and validation of designer benzodiazepines in blood and hair but fail to validate a method to detect designer benzodiazepines in oral fluid. This study focuses on the method validation of 13 designer benzodiazepines in oral fluid using …

Hair And Drugs: The Impact Of Dry Shampoo And Gel On Cocaine-Contaminated Hair, Marialejandra Faure Betancourt

Student Theses

Hair is a biological sample used in forensic toxicology to identify and quantify drug exposure. However, when interpreting analytical results, hair can be challenging due to the presence of external contamination. Previous studies have shown that cosmetic treatments remove drugs within the hair shaft decreasing their concentration. Nevertheless, not enough information is available to explain this phenomenon. This study focused to determine whether cosmetic products such as dry shampoo and gel influence the concentration of externally deposited cocaine (COC) and benzoylecgonine (BE) in different hair types/colors. Hair samples from fifteen COC-free volunteers of various hair colors/types were collected and divided …

The Impact Of Pharmacogenetics On Oral Fluid Steady State Drug Testing Results, Aliya D. Lewis

Student Theses

Pharmacogenetics refers to the relationship between phenotypic variation in metabolism and response to certain drugs. The interface of pharmacogenetics and forensic toxicology is not well explored. A major component of the opioid metabolic pathway has to do with a family of cytochromes called cytochrome P450 (CYP450). CYP450 refers to a general family of enzymes capable of catalyzing the oxidative biotransformation of lipophilic substances, CYPs are further categorized into families and sub-families (Roller, 2015; Zanger & Schwab, 2013). The gene CYP2D6 belongs to the CYP2 family which is responsible for the biotransformation of xenobiotics. This study looked at the effect of …

Elisa Validation Method For The Detection Of Ketamine In Hair, Daria A. Centonza

Student Theses

An ELISA method was developed and validated to detect ketamine in human hair samples. Ketamine is an anesthetic drug that causes memory loss, dissociative sensations, and hallucinations. Due to these adverse effects, ketamine is a common drug used in drug facilitated sexual assaults (DFSAs). It is very important to be able to detect the substances used in DFSAs over a longer period of time due to the delayed reporting of these crimes. Victims, often out of fear and from the sedative/memory loss effects of the drugs, tend to report these crimes when it is too late to use urine and …

Behavioral And Physiological Effects Of Heavy Metals On Fish: A Review And Preliminary Results, Diana V. Morales

Theses and Dissertations

Pollution, specifically heavy metal pollution, in various bodies of water has been a significant issue for decades. Research has been conducted on heavy metals and their effects on the environment, larger fish species, and humans since the 1970s (Skidmore, 1964; Adeniyi et al., 2007; Adeosun et al., 2015; Bawuro et al., 2018). It is known that zinc is a neurotoxin in some species and causes harm to the environment. It is also known that it causes harm to people if it is ingested or if they are exposed to it for long periods of time (Mahurpawar, 2015; Mizuno and Kawahara, …

Development And Validation Of A Method For The Determination Of Designer Benzodiazepines In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc-Ms/Ms), Laura C. Defreitas

Student Theses

In recent years, new designer benzodiazepines have become a challenge in forensic toxicology. These substances are analogues of the classic benzodiazepines, but their pharmacology is not well known, and many of them have been associated with overdoses and deaths. As a result, there has been a surge in efforts to develop ways to accurately test for these compounds in different biological matrices. This study focused to develop and validate a method for determining 17 new designer benzodiazepines in hair by liquid chromatography tandem mass spectrometry (LC-MS/MS). Hair samples were decontaminated, pulverized, and 20 mg of the sample was incubated in …

Cocaine, Cocaethylene And Ethanol In Postmortem Blood Submitted To The New York City Office Of Chief Medical Examiner, Jada T. Alexis

Student Theses

Cocaine overdose deaths are on the rise in the United States. This increase may be due to the co-consumption of cocaine with other drugs. When cocaine is ingested in conjunction with alcohol, a specific metabolite called cocaethylene forms. Information regarding cocaethylene, specifically its interpretive value in post-mortem cases, has not been widely studied. Data from the Office of the Chief Medical Examiner in New York City revealed that there were 195 cases in 2017 positive for cocaethylene. These cases were most likely to involve black (42.1%) males (79.5%) in Manhattan (28.2%) aged 50 - 59 (34.4%). Most of the cases …

Using Short Chain Fatty Acids To Inactivate Pseudomonas Aeruginosa Biofilms, Stephen Lee

Dissertations and Theses

Abstract

Using Short Chain Fatty Acids to Disinfect Pseudomonas Aeruginosa Biofilms

by

Stephen Lee

Background

The study of bacteria typically focuses on the planktonic or free-living single-cell state that is purely cultured in a laboratory for subsequent growth with appropriate media. Although this traditional way of growing bacteria has been paramount to the understanding of bacterial behavior, physiology, and pathogenesis, bacteria rarely exist as pure cultures of planktonic growth forms in the natural habitat. Bacterial contamination of environmental surfaces, in the form of biofilms, is a prime public health problem and causes numerous infections within the general public. Biofilms are …

Analysis Of Cannabinoids In Serum By Gc-Ms/Ms, Christie Cannarozzi

Student Theses

Due to recent changes in federal and state legislations, the availability and consumption of cannabis products have increased in the United States. The expanded use of recreational and medicinal cannabis products increases the importance of implementing sensitive and selective instrumental methods in toxicological laboratories, as legal implications may arise in forensic cases, such as driving under the influence of drugs (DUID). The purpose of this study was to perform a cross-validation for the quantitative analysis of cannabinoids (Δ9-tetrahydrocannabinol, cannabidiol, cannabinol, 11-hydroxy-Δ9-tetrahydrocannabinol, and 11-nor-9-carboxy-Δ9-tetrahydrocannabinol) in serum by gas chromatography coupled to triple quadrupole tandem mass spectrometry (GCTQ). This method was fully …

Identification And Quantification Of Classic, Prescription, And Synthetic Opioids In Hair By Liquid Chromatography Tandem Mass Spectrometry (Lc/Ms/Ms), Natalia A. Platosz

Student Theses

The current use and misuse of synthetic and prescription opioids in the US has reached epidemic status. According to the US Department of Health and Human Services, every day more than 130 people in the US die after overdosing on opioids, and 2.1 million had an opioid use disorder in 2016. Hair is becoming an alternative matrix of increasing interest in forensic toxicology to investigate drug use and abuse patterns due to its long window of detection. The focus of this project was to develop and validate a method that simultaneously detects and quantifies 27 classic, prescription and synthetic opioids …

Effects Of Mercury On The Dopamine Transporter Cell Surface Expression In Pc12 Cells, Christina Hui

Student Theses

Environmental factors, such as heavy metal exposures, have been suggested to have an impact not only on neurodegenerative disease, such as Parkinson’s disease, but also on psychostimulants abuse and their toxicity. In this study, two questions were addressed: 1) effects of mercuric chloride on parkinsonian toxicant 1-methyl-4-phenylpyridinium (MPP⁺) induced cytotoxicity and 2) effects of mercuric chloride on cell surface dopamine transporter. Pheochromocytorma cells (PC12) were treated with various concentrations of mercuric chloride (0.02~2.0 ppm) for 4 hours with and without 0.1 mM MPP⁺. Significant potentiation of toxicity was observed when there was co-treatment with 0.5 ppm …

Development And Validation Of A Lc-Ms/Ms Method For Detection And Quantification Of 18 Antidepressants In Whole Blood, Linda Kim

Student Theses

Antidepressants are one of the most commonly prescribed drugs in America, with researchers reporting one in six Americans take some form of psychiatric drugs-mostly antidepressants (NBC News, 2016). Antidepressants are often present in combination with other drugs in suicides and drug-related deaths, so a sensitive and specific method to detect and quantify antidepressants is necessary. We developed a method for the detection and quantification of 18 different antidepressants in whole blood, with a range of 2.5-900 ng/mL and LOQ of 2.5 ng/mL. Three hundred uL of blood was used and the analytes were extracted using solid-phase extraction and analyzed by …

Method Development And Validation For The Determination Of Designer Benzodiazepines In Blood By Lc-Ms/Ms, Victoria Mei

Student Theses

The misuse of designer benzodiazepines, as an alternative to prescription benzodiazepines and for drug-facilitated sexual assaults, has emerged as a growing threat, due in part to the ease of purchasing these drugs on the internet at low prices. Causing concern for safety, is the lack of dosage information resulting in users self-medicating, often leading to unintended overdoses, coma, or death at higher doses. With limited published data regarding quantification of designer benzodiazepines in forensic cases, a method was validated for the determination of thirteen and screening for two designer benzodiazepines in blood, in addition to a limited number of common …

Simultaneous Determination Of Fourteen Antipsychotic Drugs In Whole Blood By Solid Phase Extraction And Liquid Chromatography Tandem Mass Spectrometry, Theresa M. Dawe

Student Theses

Anti-psychotic drugs are commonly prescribed to patients to treat several mental conditions, such as bipolar, schizophrenia, and manic-depressive disorder. The analysis of anti-psychotic drugs in blood is a common practice in clinical and forensic toxicology, to monitor drug treatment (therapeutic drug monitoring) or to explain the cause of the impairment or intoxication in human performance and in postmortem cases. However, most of the current studies have been performed in plasma, and a limited number in blood. We developed and validated a method to confirm and quantify a panel of commonly prescribed anti-psychotic drugs in whole blood using solid phase extraction …

Analysis Of Synthetic Opioids In Postmortem Blood, Vitreous Humor, And Brain Tissue, Rachel K. Chesser

Student Theses

In the United States, the use of new synthetic opioids (e.g. fentanyl and derivatives) has become an increasing health issue with thousands of overdose deaths being observed since 2013. With the high mortality rate associated with these substances, postmortem analyses and interpretation of synthetic opioids has become extremely important. However, due to the novelty of these compounds, the available data is limited and provides challenges to toxicologists. The focus of this project was to examine the postmortem distribution of new synthetic opioids in blood, vitreous humor, and brain tissue. New methods were developed and validated to quantify 13 synthetic opioids …

Postmortem Toxicology Of New Synthetic Opiods, Marta Concheiro, Rachel Chesser, Justine Pardi, Gail Cooper

Publications and Research

One hundred fifteen Americans die every day from opioid overdose. These overdose fatalities have been augmented by the increased availability of potent synthetic opioids, such as fentanyl and its derivatives. The death rate of synthetic opioids, other than methadone, increased by 72.2% from 2014 to 2015, and doubled from 2015 to 2016, situating the USA in the midst of an opioid overdose epidemic. The analytical identification of these opioids in postmortem samples and the correct toxicological data interpretation is critical to identify and implement preventive strategies. This article reviews the current knowledge of postmortem toxicology of synthetic opioids and the …

Detection Of In-Utero Ethanol Exposure Via Etg And Ets Analysis In Umbilical Cord And Placenta, Jennifer Hanna

Student Theses

Alcohol exposure during pregnancy constitutes one of the leading preventable causes of birth defects, mental retardation and neurodevelopmental disorders in exposed children. According to the 2016 National Survey on Drug Use and Health, alcohol was the second most prevalent substance (8.3%) after tobacco (10%), being this alcohol prevalence higher among 26-44 years old pregnant women than in the 18-25 years old group (9.1 vs 6.5%) (Center for Behavioral Health Statistics and Quality, 2017). The ethanol marker ethyl glucuronide (EtG) has proven to be a specific long-term marker of ethanol in-utero exposure in meconium; however, currently there are scarce or no …

Zolpidem Facilitated Sexual Assaults: A Hair Method Validation, Danielle N. Chasworth

Student Theses

A liquid chromatography tandem mass spectrometry (LC-MSMS) method was developed and validated to detect for the presence of zolpidem in human hair samples. Zolpidem is a sedative hypnotic whose adverse effects make it a common drug found in drug facilitated crimes (DFC). It is important to be able to detect and quantitate the drug after a long period of time due to the victim’s delayed reporting of the crime. Hair’s long window of detection makes it a useful matrix for DFC investigations. The linear range of the assay was targeted at 2 pg/mg to 1,000 pg/mg and experiments designed to …

Δ-9-Thc Effect On The Dopamine Transporter, Brooke E. Nielsen

Student Theses

Understanding the mechanism behind drugs of abuse is one of the key elements to understanding why addiction is so prevalent in society. The goal of this research was to determine the effect that a popular cannabinoid, Δ -9-tetrahydrocannabinol has on the regulation of dopamine neurotransmitter in the synapses. It was hypothesized that the addictive high users experience from using Δ-9-THC had a direct effect on lowering the dopamine transporter protein on cell surface causing a buildup of dopamine in the synapse. The results of the study show that the higher concentration of Δ-9-THC that the cells were exposed to caused …

Examining The Roles Of Genetic And Environmental Factors In Drosophila Melanogaster Hematopoiesis And Innate Immune System, Minkyung Lee

Student Theses and Dissertations

Nearly 24 million people are affected by autoimmune diseases in the United States. Main causes of autoimmune diseases have been attributed to genetic predisposition and environmental exposure to chemicals such as hormones and pesticides. Due to the large population that are affected by autoimmune diseases, it is critical to understand the mechanisms behind them. In this study, we sought to explore both genetic and environmental factors that affect hematopoiesis, or the formation of specific blood cells, and immune system in Drosophila melanogaster. As Drosophila melanogaster have conserved pathways of hematopoiesis as humans, they were used as the model organism …

Regulation Of Radioactive Fracking Waste, Elizabeth Ann Glass Geltman, Nichole Leclair

Publications and Research

Natural gas extracted form shale reached record production totals in 2015 in the United States and the US Energy Information Administration (EIA) forecasts natural gas production will continue to increase. Wastes from shale gas extraction can contain the radioactive isotopes radium-226 (Ra-226) and radium-228 (Ra-228), which decay further into radon (Rn). Exposure to radon, a form of naturally occurring radioactive materials (NORM), is the leading cause of lung cancer in the United States, after smoking. This article explores how states handle the disposal of technologically enhanced naturally occurring radioactive materials (TENORM) and/or NORM waste from oil and gas operations to …

Identification And Quantification Of Cyanide And Its Metabolites In Lemur Urine, Jeremy Peralta

Student Theses

Cyanide is a chemical compound that contains the monovalent groups of carbon and nitrogen. This substance is considered a rapidly acting deadly chemical. However, some animals such as lemurs consume food products that are known to contain elevated levels of cyanide without major consequences. The mechanism by which the lemur can handle this high exposure to cyanide is unknown. In this study, we developed and validated two analytical methods for the determination of cyanide and two metabolites, thiocyanate and 2-aminothiazoline-4-carboxylic acid (ATCA) in lemur urine. The method was applied to 47 authentic lemur urine samples collected from 4 different species …

A Validation Of The Detection Of Barbiturates In Hair By Elisa, Alisa M. Valentino

Student Theses

An original method to extract and detect barbiturates, specifically secobarbital, in hair by enzyme-linked immunosorbent assay (ELISA), has been developed. Drug-free hair specimens were fortified with an exaggerated amount of secobarbital to produce a homogeneous, true positive sample to be utilized to test the drug extraction efficiency from hair. Drug extraction using hair extraction buffer (HEB) from Immunalysis was compared to a base digestion using 1M NaOH. After LCMS/MS analysis, HEB extraction was deemed a successful method for extracting barbiturates from hair. Using this method, the Barbiturates Direct ELISA Kit from Immunalysis was evaluated for its potential use in the …

Characterizing The Impacts Of Contaminants On Fish Embryogenesis And Revealing An Alternate Molecular Mechanism Of Ahr Mediated Cardiac Defects, Corinna Singleman

Dissertations, Theses, and Capstone Projects

There is a long history of damage to natural ecosystems from environmental pollution. Many environmental contaminants are man-made and have been released with abandon over the last 100 years including dioxins, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), and polychlorinated biphenyls (PCBs). These chemicals act on similar cellular processes and cause skin lesions, cancer, learning disabilities and reproductive problems in many vertebrates. There are many studies exploring various aspects of TCDD and PCB exposure on model and wild organisms. Few studies however, have compared effects of PCB mixtures on ecosystems to effects of individual PCBs in the lab. The first aim of this thesis is …

Quantitative Analysis Of Opioids And Cannabinoids In Wastewater Samples, Alethea Jacox

Student Theses

Wastewater-based epidemiology is an innovative approach that uses the analysis of human excretion products in wastewater to obtain information about exposure to drugs in defined population groups. We developed and validated an analytical method for the detection and quantification of opioids (morphine, oxycodone, hydrocodone, oxymorphone and hydromorphone), and cannabinoids (9-tetrahydrocannabinol, 11-nor 9-carboxy- tetrahydrocannabinol (THCCOOH) and THCCOOH-glucuronide) in raw influent wastewater samples by ultra-high performance liquid chromatography-tandem mass spectrometry. Method validation included linearity (5–1 000 ng/L for opioids, 10–1 000 ng/L for cannabinoids), imprecision (<21.2%), accuracy (83%–131%), matrix effect (from –35.1% to –14.7%) and extraction efficiency (25%–84%), limit of detection (1–5 ng/L) and quantification (5–10 ng/L) and auto-sampler stability (no loss detected). River, sewage overflow and wastewater samples were collected in triplicate from different locations in New York City and stored at -20 C until analysis. River water samples were negative for all the compounds. Water from sewage overflow location tested positive for morphine (10.7 ng/L), oxycodone (4.2–23.5 ng/L), oxymorphone (4.8 ng/L) and hydromorphone (4.2 ng/L). Wastewater samples tested positive for morphine (133.0– 258.3 ng/L), oxycodone (31.1– 63.6 ng/L), oxymorphone (16.0–56.8 ng/L), hydromorphone (6.8–18.0 ng/L), hydrocodone (4.0– 12.8 ng/L) and THCCOOH (168.2– 772.0 ng/L). This method is sensitive and specific for opioids and marijuana determination in wastewater samples.

Stability Of Synthetic Cathinones In Oral Fluid Samples, Briana Miller, Jiyoung Kim, Marta Concheiro

Publications and Research

Synthetic cathinones are new stimulant drugs derived from cathinone that have been sold as “legal highs” worldwide. These compounds can elicit powerful effects such as delusions, hallucinations as well as other potentially dangerous behavior. New analogs with varying effects and potencies are constantly introduced in the market to evade legislation, and they are not detected by routine screening and confirmation methods. Oral fluid is an alternative matrix of increasing interest in forensic toxicology. Its collection is non-invasive and easily supervised, and positive drug findings typically reflect recent drug exposure. The focus of this research was to develop a method for …

Bioanalysis For Cocaine, Opiates, Methadone And Amphetamines Exposure Detection During Pregnancy, Marta Concheiro, Elena Lendoiro, Ana De Castro, Eva Gonzalez-Colmenero, Ana Concheiro-Guisan, Patricia Penas-Silva, Manuel Macias-Cortina, Angelines Cruz-Landeira, Manuel Lopez-Rivadulla

Publications and Research

Drug exposure during pregnancy constitutes a major legal issue and public health concern. Drug and metabolite determination in biological matrices from mother and newborn is an objective indication of prenatal drug exposure. However, limited data are available regarding the interpretation of these analytical results in terms of window of detection and degree of exposure. We collected paired maternal hair, meconium, placenta and umbilical cord from 727 mother-newborn dyads. We analyzed these specimens by liquid chromatography tandem mass spectrometry for the determination of cocaine, opioids, methadone and amphetamines, and compared the analytical results from the four different matrices. The cases were …

Analysis Of Synthetic Cannabinoids And Drugs Of Abuse Amongst Hiv-Infected Individuals, Jillian M. Wetzel

Student Theses

Synthetic cannabinoids are man-made mind-alternating chemicals. Law enforcement and legislation have attempted to classify many of these synthetic cannabinoids as schedule I controlled substances, however, they are continuously being modified by dealers at the retail end of the distribution chain. Addiction and moderate use of illicit drugs have been identified as major reasons for non-adherence to antiretroviral therapy among HIV patients. However, there is no data regarding the impact of synthetic cannabinoid exposure in this population and how this affects their compliancy with taking antiretroviral therapy. A total of 72 authentic urine specimens were collected weekly from 13 individuals with …

Synthetic And Biological Exploration Of (+)-Boldine - Identification Of Potential Cns Receptor Ligands, Sujay Joseph

Theses and Dissertations

(+)-Boldine, an aporphine alkaloid, is reported to be biologically active at various Central Nervous System(CNS) receptors. However, only a few Structure Activity Relationship(SAR) studies have been conducted using boldine’s aporphine scaffold. A library of novel analogs was synthesized from boldine to understand the effect of bisbenzylation at C2 and C9 positions on the affinity and selectivity at the serotonin receptors.

The Smell Of Hopelessness, Juline Cariba Rachel Party

Capstones

Rafts of sargassum seaweed kilometers wide have been invading the Caribbean for more than five years, but 2015 was the worst. Tons of seaweed stretch from Texas south to Trinidad and Tobago, with the Lesser Antilles suffering the most damage. Residents near beaches are exposed to an insidious and pernicious danger, scientists say, from fumes that smell like rotten eggs, emitted by the decaying algae. The odor also drives tourists away from beaches and restaurants, and the tourism economy is collapsing.Amid the algae crisis, an elderly woman, Virginie Mark, is trying to survive. She struggles with her health, finances and …