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Literature
MecStatSM Literature
MecStatSM Alcohol Literature
HairStatSM Literature
UrineStatSM Literature
OralStatSM Literature
MedPro Literature
MECSTATSM LITERATURE
Journal of Chromatography B, 713 (1998) 137-146
Determination of drugs of abuse in meconium.
Christine Mooreª, Adam Negruzb, Douglas Lewisª
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
bUniversity of Illinois at Chicago, Department of Pharmaceutics and Pharmacodynamics, College of Pharmacy, 833 S. Wood Street, Chicago, IL 60612, USA
Fetal exposure to drugs has many adverse effects upon the neonate including low birthweight, small head size and an increased risk of miscarriage and death. Correct diagnosis of drug use during pregnancy is essential if the child is to receive specialized treatment and care, which will aid in learning and behavioral development. Diagnosis will also help in the prevention of subsequent drug-exposed children being born to the same mother. Meconium is the first fecal material excreted by the newborn and is an excellent depository for drugs to which the fetus has been exposed. Its analysis is widely accepted in the scientific and medical communities since it has several advantages over urinalysis, including providing a longer historical record of drug exposure and easier collection. Various drugs and their metabolites have been detected in meconium, however, the metabolic profile of drugs in meconium differs from that of neonatal and/or maternal urine. This article addresses the determination of cocaines, amphetamines, opiates, cannabinoids, phencyclidine, nicotine and methadone in meconium using several analytical procedures including immunochemical and chromatographic methods.
J Anal Toxicology. 1996 Jan-Feb;20(1):50-1.
The determination of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH) in meconium.
CMoore C, Lewis D, Becker J, Leikin J.
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
The determination of 11-nor-delta 9-tetrahydrocannabinol-9-carboxylic acid (THCCOOH), the major urinary metabolite of delta 9-tetrahydrocannabinol (THC), in meconium is extremely difficult because of the high concentration of lipids in the specimen and the low concentration of drug present. A simple, robust, analytical procedure for the screening and confirmation of THCCOOH in meconium is presented. To our knowledge, the procedure is the first published method for the successful confirmation of THCCOOH in meconium and is used routinely in our laboratory for the purpose of detecting marijuana use during pregnancy.
J Anal Toxicology. 1995 Oct;19(6):514-8.
The detection of hydrocodone in meconium: two case studies.
Moore CM, Deitermann D, Lewis D, Leikin J.
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
The detection of hydrocodone in meconium samples is reported for the first time. Hydrocodone, a semisynthetic antitussive and analgesic, is often prescribed as a painkiller following minor surgery or dental work. It also cross-reacts in enzyme and fluorescence polarization immunoassay opiate systems. In two cases recently received by our laboratory, hydrocodone was detected following a positive opiate immunoassay screening result. The meconium samples were not hydrolyzed because previous work in our laboratory showed that greater than 70% of morphine in meconium is not glucuronide bound. The confirmatory procedures showed that, in case No. 1, codeine was also detected but at a much lower concentration than the hydrocodone. In case No. 2, morphine was detected but, again, at a much lower concentration than the hydrocodone. Even though in both samples another opiate was also detected, the possibility still remains that a positive opiate test result may be reported by screen-only laboratories based solely on the presence of hydrocodone. We present a novel extraction method and a gas chromatographic-mass spectrometric confirmatory procedure for the determination of hydrocodone and hydromorphone in meconium.
Vet Hum Toxicology. 1995 Aug;37(4):318-9.
Multiple birth concordance of street drug assays of meconium analysis.
Lewis D, Moore C, Leikin JB, Kechavarz L.
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
To determine the prevalence of maternal drug usage in a mid-size midwestern city (population 250,000), we analyzed 1,175 consecutive meconium samples from the neonatal intensive care unit from March 1991 through December 1993. We focused on meconium assays from multiple births as a quality control method. Meconium specimens were analyzed using fluorescence polarization immunoassay (FPIA-Abbott Diagnostics) with confirmation done by gas chromatography/mass spectrometry (GC/MS). Cutoff concentrations of 5 ng/g were utilized for all analytes. A total of 151 samples (12.9%) tested positive. Cocaine-exposed neonates had the highest positive rate (63 or 5.4%), followed by marijuana (52 cases or 4.4%), cocaethylene (12 cases or 1%), and amphetamine (1 case or 0.1%). Nine patients (0.8%) had multiple drugs present. There were a total of 23 sets of multiple births (21 twins, 2 triplets); 20 sets of multiple births (42 patients) had concordance with all births testing negative. Three sets of twins had concordance in testing positive, with 1 twin testing positive for cocaine while the other twin tested positive for cocaine and marijuana. No absolute discordance of twins assays were noted. The rate of maternal drug use through measurement of meconium is about 12.95% in this mid-sized midwestern city. Twin studies provide an excellent method for verifying fetal drug exposure. The use of sets of multiple births provides a unique internal quality control mechanism in determining fetal drug exposure.
J Anal Toxicology. 1995 May-Jun;19(3):148-50.
Meconium analysis for cocaine: a validation study and comparison with paired urine analysis.
Lewis DE, Moore CM, Leikin JB, Koller A.
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
We established the validity of a drug-screening method to detect the presence of cocaine or benzoylecgonine or both in meconium and then undertook an analysis of results from urine and meconium specimens obtained concurrently from neonates within 3 days of birth. Meconium specimens from 82 consecutive newborns were analyzed using fluorescence polarization immunoassay (FPIA), Kinetic Interaction of Microparticles in Solution (KIMS), and gas chromatography-mass spectrometry (GC-MS). Each meconium specimen was analyzed by all three methods. Fifty-four paired urine and meconium specimens were obtained over a 13-month period from a neonatal intensive care unit. Urine drug testing was performed by immunoassay (enzyme multiplied immunoassay [EMIT] technique), whereas meconium specimens utilized FPIA with GC-MS confirmation on all but one specimen (due to insufficient quantity). Ten true positives were found by GC-MS, 10 positives were found by FPIA, and 70 positives were found by KIMS. Of the 54 paired samples, 39 samples tested negative for cocaine in both urine and meconium; four specimens were positive by both routes; 10 specimens were negative in urine but positive in the meconium; and one specimen tested positive in urine but negative in the meconium. Thus, 9.3% of the urine specimens tested positive, and 25.9% of meconium samples tested positive (p = .011; McNemar's Test). We conclude that screening meconium specimens by FPIA followed by GC-MS confirmation of screened positives yields highly accurate determinations of the presence of cocaine or benzoylecgonine or both in meconium and that testing of meconium for cocaine and its metabolites is more sensitive than testing of urine.
J Toxicol Clin Toxicology. 1994;32(6):697-703.
Cocaethylene in meconium specimens.
Lewis DE, Moore CM, Leikin JB.
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
Cocaethylene, a metabolite of cocaine and ethanol, exhibits cardiac and neurobehavioral effects. In order to determine the prevalence of this compound in meconium specimens, samples which gave a positive result for benzoylecgonine using fluorescence polarization immunoassay were analyzed by gas chromatography/mass spectrometry for cocaine, cocaethylene and benzoylecgonine. Deuterated cocaine, cocaethylene and benzoylecgonine were used as internal standards. Gas chromatography/mass spectrometry cutoff concentrations of 5.0 ng/g were utilized for all analytes. Of the 361 specimens which consecutively confirmed positive for cocaine or benzoylecgonine, 114 (31.6%) tested positive for cocaethylene. Further, cocaethylene accumulates in greater concentrations in meconium than urine, and is a useful analyte for identifying fetal alcohol exposure.
Forensic Science International 1999 Jun 28;102(2-3):167-71.
The detection of cotinine in hydrolyzed meconium samples.
Dempsey D, Moore C, Deitermann D, Lewis D, Feeley B, Niedbala R
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
San Francisco Bay Area Regional Poison Control Center, CA, USA.
To date, the screening of meconium for the determination of tobacco exposure in newborns has proven difficult. It was hypothesized that cotinine forms reversible Schiff base bonds with free amino functions on proteins, therefore, hydrolysis of meconium would be necessary for the detection of 'free' cotinine. One-hundred-and-two (102) meconium samples received into our laboratory were extracted using a routine non-hydrolysis screening procedure for drugs of abuse. Separate aliquots of the specimens were hydrolyzed and re-extracted according to the same procedure. The results of the two methods were compared using a highly specific cotinine micro-plate enzyme immunoassay procedure (EIA). Of the non-hydrolyzed samples, 33% were positive for cotinine, while 79% of the hydrolyzed samples were cotinine-positive. Common drugs of abuse did not interfere with the analysis. Micro-plate EIA provides a rapid, simple and reliable screening method for the determination of cotinine in meconium following hydrolysis and extraction. In general, the meconium specimens received into our laboratory are from newborns considered to be at risk for post-natal problems due to suspected drug and/or alcohol abuse during pregnancy.
Neonatal Intensive Care September/October 1994 p.24
Incorrect Diagnosis of Cocaine-Exposed Babies: A Report.
Douglas Lewis, Christine Moore, Jerrold Leikin
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
Meconium testing as an alternative to neonatal urine analysis for the determination of drug exposure during pregnancy is becoming increasingly popular in the medical community.
Meta-hydroxybenzoylecgonine (m-OH-BZE), a minor urinary metabolite of cocaine in adult, has only recently been reported as having sufficient immunoreactivity to cause inconsistent data in meconium screening processes. The analysis of two hundred and eight (208) consecutive meconium samples for m-OH-BZE, benzoylecgonine (BZE) and cocaine revealed that twenty-three percent (23%) of the samples contained only
m-OH-BZE and none of the other analytes. Since m-OH-BZE is not a routine analyte in most hospital and commercial meconium reference testing laboratories, almost a quarter of cocaine exposed babies are potentially being wrongly diagnosed because only
m-OH-BZE is present.
Journal of Analytical Toxicology, Vol. 29, January/February 2005
The Detection of Oxycodone in Meconium Specimens.
Ngoc Lan Le, Andrea Reiter, Kimberly Tomlinson, Joseph Jones, Christine Moore
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
A procedure for the determination of oxycodone in meconium using direct ELISA microplate technology followed by electron impact gas chromatography-mass spectrometry (GC-MS) is described for the first time. The abuse of oxycodone (OxyContin™) has been widely discussed in mainstream media, and it has been described as a cheap form of heroin. Oxycodone has been reported as having a high degree of abuse and potential complications in neonates from maternal drug use. Using a standard enzyme multiplied immunoassay screening technology, the cross-reactivity of oxycodone to the morphine antibody is only 5-6%. A positive screening value would require a high concentration of drug to be present, so a protocol for the detection of oxycodone in meconium using a direct ELISA microplate immunoassay followed by
GC-MS was developed. The assay is now routinely used in our laboratory.
Journal of Analytical Toxicology, Vol. 17, October 1993
m-Hydroxybenzoylecgonine: An Important Contributor to the Immunoreactivity in Assays for Benzoylecgonine in Meconium.
Bernard W. Steele, Emmalee S. Bandstra, Niou-Ching Wu
Departments of Pathology and Pediatrics, University of Miami/Jackson Memorial Medical Center, Miami, FL
George W. Hime
Dade County Medical Examiner Department, Miami, FL
W. Lee Hearn
Dade County Medical Examiner Department and the Departments of Pharmacology, Pathology, and Epidemiology and Public Health, University of Miami, Miami, FL
Meconium has been reported to be a more suitable specimen than maternal or neonatal urine for detecting fetal exposure to cocaine. In a study comparing various immunoassays with gas chromatography/mass spectrometry (GC/MS), several unexplained discrepancies among the assays were noted. Using methanol extracts of meconium samples, an immunoreactive spot that was more polar than benzoylecgonine was detected by thin-layer chromatography (TLC). An extract of this spot analyzed by GC/MS yielded a fragmentation pattern indicative of an aryl hydroxylated benzoylecgonine. Standards of m-hydroxybenzoylecgonine, o-hydroxybenzoylecgonine, and p-hydroxybenzoylecgonine were synthesized. It was determined that
m-hydroxybenzoylecgonine had the same retention time and ion ratios as the TLC immunoreactive spot. Furthermore, m-hydroxybenzoylecgonine proved to be immunoreactive. Ten meconium samples immunoreactive for benzoylecgonine were analyzed by GC/MS. Results before and afer hydrolysis with B-glucuronidase (type IX) showed free m-hydroxybenzoylecgonine comprising 59 to 94% of the total
m-hydroxybenzoylecgonine and showed total m-hydroxybenzoylecgonine values ranging from 0.2 to 6.3 times as high as benzoylecgonine. Therefore,
m-hydroxybenzoylecgonine appears to be a quantitatively important cocaine metabolite in meconium, which is responsible for a significant portion of the discrepancy between benzoylecgonine concentrations in meconium extracts as measured by immunoassay and GC/MS.
MECSTAT ALCOHOL LITERATURE
Ther Drug Monit. 21(6).1999 p.644
Fatty Acid Ethyl Esters: A Novel Biologic Marker for Heavy In Utero Ethanol Exposure: A Case Report.
Klein, Julia; Karaskov, Tatyana; Koren, Gideon
Departmnet of Pediatrics, Division of Clinical pharmacology/Toxicology, The Hospital for Sick Children, and CIBC Wood Gundy Children’s Miracle Foundation Chair in Child Health Research, the University of Toronto, Toronto, Ontario, Canada
Received May 13, 1999; accepted August 11, 1999
Address correspondence and reprint requests to Gideon Koren, MD, FACCT, FRCPC, Division of Clinical Pharmacology/Toxicology, The Hospital for Sick Children, 555 University Avenue, Toronto, Ontario, Canada.
Summary: The authors report testing the meconium of a newborn for the presence of FAEE. Meconium from a newborn of a woman who acknowledged drinking beer throughout pregnancy was tested. The authors also tested the meconiums of 3 newborns whose mothers did not drink at all while pregnant. The FAEE were extracted from the meconium samples using solid phase extraction (SPE), and were identified and quantitated by gas chromatography with flame ionization detection (FID). For assignment of retention times and determination of individual concentrations, authentic mixtures of FAEE were injected. The total FAEE concentration in the meconium of the alcohol-exposed infant was 13126 ng/g compared to a mean of 410 ng/g in the control meconiums. Also, in this case, palmitic, linoleic, and stearic ethyl esters were found in the alcohol-exposed infant’s meconium while they were not found in the unexposed infant’s meconium. In the parallel experiment, the authors spiked increasing amounts of ethyl alcohol (0-40mM) into the meconium from a newborn that was not exposed to ethanol in utero. The spiked samples were incubated for 4 hours at 37°C and subsequently assayed for the presence of ethyl linoleate. In these experiments, they document for the first time that FAEE is produced in meconium. If confirmed by large studies, FAEE may become the first neonatal biologic marker for babies at risk for alcohol-related birth defects.
Clinical Chemistry 49:1 P.133-136 (2003)
Prevalence of Fatty Acid Ethyl Esters in Meconium Specimens.
Christine Moore¹, Joseph Jones¹, Douglas Lewis¹, and Karen Buchi²
US Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, IL 60018, USA
Background: Fetal alcohol syndrome (FAS), alcohol-related birth defects (ARBDs), and alcohol-related neurodevelopment disorders (ARNDs) in neonates are often the result of maternal alcohol consumption during pregnancy. Facial characteristics are associated with FAS, but ARBDs and ARNDs are more difficult to diagnose. Fetal exposure to alcohol can cause central nervous system dysfunction, pre-and postnatal growth problems, cardiac defects in neonates, and attention deficit disorders and mental retardation in older children. To date, diagnosis of fetal alcohol effect has depended largely on maternal interview, although clinical tests are becoming more widely used. Fatty acid ethyl esters (FAEEs) are formed in the body by esterification of glycerides and have been detected in the meconium of newborns. This report estimates the prevalence of fetal alcohol exposure in two populations by detecting FAEEs in meconium.
Methods: We analyzed the prevalence of FAEEs in the meconium of two separate groups of neonates by use of solid-phase extraction and analysis by gas chromatography-mass spectrometry in the chemical ionization mode. In the first study, meconium samples were taken anonymously from babies born in large, regional perinatal center in Hawaii. In the second study, specimens were obtained from infants admitted to six different newborn intensive care units within the state of Utah.
Results: In the first study, 73 of 436 (16.7%) meconium specimens tested were considered positive for FAEEs. When broken down into quartiles, the mean total FAEEs measured were 1059, 3133, 6628, and 62115 ng/g. In the second study, 35 of 289 (12.1%) specimens were considered positive. When broken into quartiles, the mean total FAEEs were 1139, 3067, 7674, and 50 143 ng/g. The overall FAEE profiles of the two study sets were remarkably similar.
Conclusion: In an adequate meconium specimen, a total FAEE concentration > 10 000 ng/g may indicate that the newborn has been exposed to significant amounts of alcohol during pregnancy.
HAIRSTATSM LITERATURE
Therapeutic Drug Monitoring, Volume 18(4).August 1996.456-459
Judicial Acceptance of Hair Tests for Substances of Abuse in the United States Courts: Scientific, Forensic, and Ethical Aspects.
Huestis, M.
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, Maryland
Summary: Changes in the acceptance of hair test results in the United States courts have resulted from two factors: the rapidly evolving scientific understanding of hair test data; and modification of the admissibility standards for forensic evidence in United States courts. The scientific, forensic, and ethical aspects of drug testing in hair impact the acceptance of hair test results. Our knowledge and experience with this new analytical technology have been developing rapidly, although there are many unanswered questions that influence acceptance of data. A consequence of the recent U.S. Supreme Court decision to have the Federal Rules of Evidence take precedence over the Frye standard in the admissibility of scientific evidence has enabled judges to determine if evidence will assist in obtaining a fuller understanding of a given case. A summation of the scientific, forensic, and ethical aspects of judicial acceptance of hair test results may be: If hair test results are positive, have we proven beyond a reasonable doubt and/or demonstrated that the preponderance of evidence supports a finding of drug use? In general, recent court decisions indicate that hair test results provide information that the courts should consider. However, unresolved scientific, forensic, and ethical issues may have a greater effect on the weight applied to hair test evidence rather than its admissibility in future court proceedings.
Forensic Science International 147 (2005) 21-24.
Correlation of Methamphetamine Results and Concentrations between Head, Axillary, and Pubic Hair.
Eunyoung Han*, Wonkyung Yang, Jaesin Lee, Yonghoon Park, Eunmi Kim, Miae Lim, Heesun Chung
Department of Narcotics Analysis, National Institute of Scientific Investigation, Seoul, South Korea
This study was designed to compare the qualitative results and concentrations of
methamphetamine (MA) and its metabolite amphetamine (AP) in head hair and hair collected
from different parts of the body (axillae and pubis). Hair from subjects (N = 14) suspected MA
users was simultaneously collected. Hair preparation involved washing step, fine cutting,
overnight extraction, derivatization by the trifluoroacetic anhydride, and gas chromatography/mass
spectrometry (GC/MS) using selective ion monitoring.
In this study, we found a good correlation of the qualitative results for MA between head hair and
hair on other parts of the body, but there were some differences in concentrations of MA and AP.
Namely, the concentrations of MA and AP were higher in axillary and pubic hair than in
head hair.
The Journal of Pharmacology and Experimental Therapeutics. 313:909-915, 2005.
Dose Related Distribution of Codeine, Cocaine, and Metabolites into Human Hair following
Controlled Oral Codeine and Subcutaneous Cocaine Administration.
Karl B. Scheidweiler, Edward J. Cone, Eric T. Moolchan, and Marilyn A. Huestis
Chemistry and Drug Metabolism, Intramural Research Program, National Institute on Drug Abuse,
National Institutes of Health, Baltimore, Marylandand ConeChem Research, LLC, Severna Park,
Maryland (E.J.C.)
Hair testing for the determination of drug exposure has many useful applications. Drug
incorporated into hair can be found for extended periods following drug exposure. There
are few controlled drug administration studies investigating drug distribution into
human hair. Ten volunteers participated in a 10-week controlled cocaine and codeine
administration study while residing in the secure research ward. Weekly hair samples
were collected by electric razor. During the low-dose week (week 4), volunteers
received 75 mg/70 kg cocaine subcutaneously and 60 mg/70 kg codeine orally on alternating
days, a total of three doses for each drug. Similarly, during week 7, volunteers received
three doses 150 mg/70 kg cocaine and 120 mg/70 kg codeine. Maximum hair concentrations (Cmax)
were found 1 to 3 weeks after low and high doses. Dose-related Cmax values of cocaine,
benzoylecgonine, ecgonine methyl ester, norcocaine, cocaethylene, and codeine were found
following low and high doses. Hair analysis was performed using liquid chromatography tandem
mass spectrometry. A positive linear relationship was found between total melanin content of
hair and Cmax of codeine, cocaine, and metabolites following high dosing. This study
demonstrated dose-related concentrations of cocaine and metabolites in human hair following
controlled cocaine administration. These data are the first demonstrating melanin-related
incorporation of cocaine and metabolites into human hair following controlled cocaine
administration.
Journal of Analytical Toxicology. Vol 25, pp. 555-558. 2001.
The Determination of 11-nor-D9-THC-9-carboxylic acid (THC-COOH) in Hair
Using Negative Ion Gas Chromatography-Mass Spectrometry and High-Volume Injection
Thomas Donahue
Omega Laboratories
Christine Moore, and Frank Guzaldo
United States Drug Testing Laboratories, Inc
The determination of 11-nor-D9-THC-9-carboxylic acid (THC-COOH) in hair specimens at the
sensitivity required to detect marijuana users is a difficult analytical problem. A sensitive
and specific method has been developed for the quantitative assay of THC-COOH in hair. Hair
specimens were washed, incubated in sodium hydroxide, subjected to solid-phase extraction,
and analyzed using high-volume injection coupled with negative chemical ionization (NCI)
mass spectrometry. A common disadvantage of chemical ionization, the production of a single
mass-to-charge ratio ion, was also addressed. By specific selection of the derivatizing
agent, three ions were monitored, allowing the calculation of two ion ratios, as in electron
impact mode. The method was applied to several hair specimens taken from known marijuana
users and workplace specimens. This is the first publication describing the use of high-volume
injection and NCI mass spectrometry for the determination of THC-COOH in hair.
Journal of Analytical Toxicology, Vol. 20, January/February 1996
Incorporation of Isotopically Labeled Cocaine and Metabolites into Human Hair: 1. Dose-Response Relationships
Gary L. Henderson*, Martha R. Harkey, and Chihong Zhou
Department of Medical Pharmacology and Toxicology; School of Medicine, University of California, Davis, CA 95616
Reese T. Jones and Peyton Jacob, III
Langley Porter Institute, University of California, San Francisco, CA 9414.3
Deuterium-labeled cocaine (cocaine-d5) was administered intravenously and/or intranasally in
doses of 0.6-4.2 mg/kg to 25 human volunteers under laboratory clinical conditions. Sequential
blood samples were collected for up to 3 days, and hair samples were collected for up to 10 months.
Samples were analyzed by gas chromatography-mass spectrometry (GC-MS) for cocaine-ds and its
major metabolite, benzoylecgonine-d5 (BZE-d5). The parent drug, cocaine-d5, was the predominant
analyte in hair, whereas BZE-d5 was the major analyte in blood, especially at later time periods.
The amount of cocaine-d5 incorporated into hair ranged from 0.1 to 5 ng/mg hair, whereas the
amount of BZE-d5 was approximately one-sixth of that concentration. The threshold dose for
detection was estimated to be 25-35 mg of drug administered intravenously. A single dose could
be detected for 2-6 months. Subjects receiving the same dose differed (from two to 12 times as
much depending upon how it was measured) in the amount of cocaine-d5 incorporated into their
hair. Non-Caucasians, in particular, incorporated more cocaine-d.5 in hair than did Caucasians.
Also, segmental analysis of the samples revealed considerable intersubject variability in the
time drug first appeared in hair and the rate at which the drug moved along the hair shaft
with time. These interindividual differences could not be explained by differences in plasma
pharmacokinetics. Considered together, these results suggest that cocaine incorporation into
hair may occur by way of multiple mechanisms-by way of sweat and sebum, for example-and at
various times during the hair growth cycle, Thus, hair analysis using GC-MS appears to be a
very sensitive method for detecting cocaine ingestion. However, within the range of doses
used in the present study, hair does not provide a particularly accurate record of either the
amount, time, or duration of drug use.
Journal of Analytical Toxicology, Vol. 26, April 2002
The Simultaneous Determination of Codeine, Morphine, Hydrocodone, Hydromorphone, 6-Acetylmorphine, and Oxycodone in Hair and Oral Fluid
Joseph Jones, Kimberly Tomlinson, and Christine Moore
U.S. Drug Testing Laboratories, 1700 S. Mount Prospect Road, Des Plaines, Illinois 60018
Recently, the abuse of prescription opiates as alternatives to heroin has become a national concern.
The determination of a six-drug opiate panel, codeine, morphine, 6-aceiylmorphine, hydrocodone,
hydromorphone, and oxycodone, in hair and oral fluid using solid-phase extraction and capillary
gas chromatography-mass spectrometry (GC-MS) is described. Oral fluid was obtained from the
donor by insertion of absorptive collectors into the mouth. Hair was collected from the patient
and powdered using stainless steel ball bearings in a mini bead-beater apparatus. Opiates present
in the samples were extracted from a buffered, aqueous matrix with a solid-phase cartridge. The
extracts were concentrated and the methoxime-BSTFA derivatives prepared in order to eliminate
interference from the ketooopiates. The extracts were separated by GC-.MS in electron impact mode.
By utilizing methoxyamine, we were able to produce methoxime derivatives required for single
derivative production and chromatographically separate all six opiates. The routine analysis of these
opiates in hair and oral fluid using GC-MS is described for the first time.
URINESTATSM LITERATURE
J Am Soc Mass Spectrom. 15 (2004) 188-193.
Confirmatory Analysis of Ethylglucuronide in Urine by Liquid-Chromatography/Electrospray
Ionization/Tandem Mass Spectrometry According to Forensic Guidelines.
Wolfgang Weinmann, Patrick Schaefer, and Annette Thierauf Institute of Legal Medicine,
Forensic Toxicology, University Hospital, Freiburg, Germany
Andre Schreiber
Applied Biosystems, Darmstadt, Germany
Friedrich Martin Wurst
Psychiatric University Clinic, Basel, Switzerland
B-D-ethylglucuronide (EtG) is a stable Phase II metabolite of ethanol which can be detected
in urine samples several days after elimination of ethanol. It is a useful diagnostic
parameter for monitoring abstinence of alcoholics in alcohol withdrawal treatment.
For this purpose, mass spectrometric identification and detection of controlled substances
in more sensitive fields such as forensic toxicology, workplace drug testing, doping
analysis, and veterinary organic residue control, official guidelines have been released
requiring a chromatographic separation and a minimum of two mass spectrometric transitions
of the analyte. However, for detection of EtG none of the published LC-MS/MS methods
could fulfill the minimum requirements of any of these guidelines. Therefore, an existing
LC-MS/MS method has been modified by monitoring further MS/MS transitions instead of only
one (deprotonated molecule [M-H]-/product ions: m/z 75, 85, 113, and 159 optional) with
the aim of withstanding administrative or court scrutiny in forensic or workplace drug
testing cases. Full method validation has been performed in accordance to guidelines of
the German Society of Toxicology and Forensic Chemistry (GTFCh) and requirements of
ISO 17025. One application field in the United States is a workplace monitoring program
to detect surreptitious alcohol use among recovering health professionals, who by contract
had agreed on total abstinence after drug and alcohol withdrawal therapy.
Journal of Analytical Toxicology 29 (2005) 270-274
Ethyl Sulfate: A Metabolite of Ethanol in Humans and a Potential Biomarker of Acute Alcohol Intake.
Anders Helander and Olof Beck
Karolinska Institutet and University Hospital, Stockholm, Sweden
This study identified ethyl sulfate (EtS) in human urine and compared the excretion
characteristics of EtS with that of ethanol and ethyl glucuronide (EtG). Urine samples
were collected from healthy subjects after a single ethanol dose, and also selected
from routine clinical samples. Simultaneous analysis of EtS and EtG was performed by direct
electrospray liquid chromatography-mass spectrometry in the negative ion mode, with
selected-ion monitoring of the pseudomolecular ions at m/z 125 for EtS (MW 126 g/mol)
and m/z 221 for EtG (MW 222 g/mol). The identity of EtS in authentic urine specimens was
established by co-chromatography with reference substance, the presence of product
ions (m/z 97 and 80 from m/z 125) with correct relative intensity, and a correct sulfur
isotope ratio for 34S (m/z 127). After healthy subjects drank ethanol, EtS showed a much
longer, dose-dependent elimination half-life than the parent compound.
No EtS was detected in urines collected after abstention of ethanol for several days prior
to sampling. Among 354 consecutive clinical samples, 86 were positive for both
EtS and EtG with a mean EtG/EtS molar ratio of 2.3 (median 1.7). Another three urine
samples were only positive for EtS and four only for EtG. The present results confirm
that sulfate conjugation is a normal but minor metabolic pathway for alcohol intake.
It is also indicated that the concurrent determination of EtS and EtG will improve
sensitivity, when being used as biomarkers of recent drinking.
ORALSTATSM LITERATURE
MEDPRO LITERATURE
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