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R L Fitzgerald

Publications and source records attributed to R L Fitzgerald.

31 records · Page 2Linked to original sources
PubMed1994

Detecting benzodiazepines: immunoassays compared with negative chemical ionization gas chromatography/mass spectrometry.

We tested 231 urine samples by six immunoassay methods--EMIT d.a.u., EMIT II, Roche Abuscreen Online, Abbott TDx, Diagnostic Products Corp. (DPC) double-antibody radioimmunoassay (RIA), and Biosite Triage--and by negative chemical ionization gas chromatography/mass spectrometry to determine how the immunoassays performed on samples selected for suspected benzodiazepine use (n = 100) and in random urine drug screening (n = 131). In general, all of the assays were successful in detecting oxazepam and related metabolites, even at concentrations below the stated cutoffs. However, the negative predictive value of benzodiazepine immunoassays for samples selected for suspected benzodiazepine use ranged from 86% to 96%. A primary difference between the test kits was the ability of DPC RIA and Triage to detect lorazepam when other assays did not. Contrary to previous reports, pretreatment of specimens with glucuronidase was not necessary to detect oxazepam-related metabolites with these immunoassays.

Benzodiazepines↗
PubMed1993

EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. I. Stereoselectivity and clinical evaluation.

The stereoselectivity, cross-reactivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine(A)/methamphetamine (MA) immunoassay (EM) were evaluated. The cut-off calibrator of the assay was 1000 ng/ml S(+)MA. Analysis of drug-added urines and 72 clinical specimens demonstrated a cut-off for S(+)-amphetamine of approximately 400 ng/ml. The stereoisomeric selectivity of the assay was determined in a concentration vs. response manner by adding pure S(+) or R(-)isomers of A and MA, to drug free urine. The EM assay demonstrated a high selectivity for S(+)-isomers with only one of 16 urine specimens collected following excessive use of nasal inhalers yielding a positive result. This specimen contained 6000 ng/ml R(-)MA. Five-hundred clinical urine specimens were simultaneously analyzed for A or MA by the EM and EMIT-d.a.u. polyclonal (EP) amphetamine assay with 131 positive results confirmed by GC/MS. In five specimens negative by EM while positive by EP, MA was present at concentrations below the 1000 ng/ml cut-off. Two ME false positive results were apparently caused by chlorpromazine (CPZ) metabolites. A study of other phenothiazines or their metabolites gave no false positive results. The possible cross reactivity of the EM assay was further studied for phenyl-isopropylamine analogs or drugs previously reported to react with the EP assay. The EM assay showed much less cross-reactivity than EP to all drugs tested.

Amphetamine↗
PubMed1993

EMIT-d.a.u. monoclonal amphetamine/methamphetamine assay. II. Detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA).

The cross-reactivity, stereoselectivity and clinical performance of the EMIT-d.a.u. monoclonal amphetamine/methamphetamine immunoassay (EM) for the detection of methylenedioxyamphetamine (MDA) and methylenedioxymethamphetamine (MDMA) in urine was evaluated. The cut-off concentrations of racemic MDA and MDMA were found to be approximately 800 ng/ml and 3000 ng/ml, respectively. The EM assay demonstrated a high selectivity for the S(+) isomer of both MDA and MDMA. Urines collected over a 24-h period from rats administered 20 mg i.v. racemic MDMA were all positive when analyzed by the EM assay. The EM was found vastly superior to the EMIT d.a.u. polyclonal amphetamine/methamphetamine assay for the detection of MDA and MDMA. The EM assay displayed sufficient sensitivity for detection of these drugs following clinical intoxication.

3,4-Methylenedioxyamphetamine↗
PubMed1993

Benzodiazepine analysis by negative chemical ionization gas chromatography/mass spectrometry.

The application of gas chromatography/mass spectrometry (GC/MS) for the simultaneous quantitation of seven commonly encountered urinary benzodiazepine metabolites is described. After comparison of the signal-to-noise ratios of high mass ions of benzodiazepines using electron impact (EI), positive chemical ionization (PCI), and negative chemical ionization (NCI), NCI was chosen because of its increased sensitivity, which ranged from four to several thousand times that of either PCI or EI. This method is novel because NCI spectra for many of these compounds have not been described. For quantitation of benzodiazepines in urine, sample preparation consisted of enzymatic hydrolysis, liquid-liquid extraction, and reaction with a silylating reagent to form trimethylsilyl derivatives. The extraction efficiency of the method was greater than 70% (range, 73-89%) for nordiazepam, oxazepam, temazepam, lorazepam, N-1-hydroxyethylflurazepam, alpha-hydroxyal-prazolam, and alpha-hydroxytriazolam; the linear range for these compounds was from 50 to 2000 ng/mL. Within-run precision was less than 6% for all analytes in the range 50-2000 ng/mL; however, run-to-run precision ranged from 3 to 21%, depending on the analyte and concentration. Quantitation was based on area ratio of high mass ions relative to deuterated internal standards, acquired by scanning the mass range from m/z 250 to 450. Because these studies were performed in the scan mode, if desired, the sensitivity could be increased by using selected ion monitoring.

Benzodiazepines↗
PubMed1993

Fatality due to recreational use of chlorodifluoromethane and chloropentafluoroethane.

Reports on fatalities of chlorofluorocarbons usually involve chlorotrifluoroethane, trichlorofluoromethane, dichlorodifluoromethane or chlorodifluoromethane, where analysis was done using packed column gas chromatography. In this case a death was caused by an azeotropic mixture of chlorodifluoromethane and chloropentafluoroethane, a combination that has not previously been reported in the forensic literature. This report details the analysis using mass selective detection employing capillary gas chromatography columns currently used in many toxicology laboratories. Postmortem toxicology revealed blood concentrations of chlorodifluoromethane and chloropentafluoroethane of 71 mg/L and 0.30 mg/L, respectively. Brain, liver, and lung concentrations of chlorodifluoromethane were (mg/kg) 2.8, 4.4, and 1.6, respectively. Brain, liver, and lung concentrations of chloropentafluoroethane were (mg/kg) 0.80, 0.80, and 0.11, respectively. The victim's blood contained 5.5 mg/L caffeine. Lidocaine, used in resuscitation attempts, was also present in the victim's blood. No other alkali-extractable drugs or volatile alcohols were detected in the victim's blood. The cause of death was acute respiratory arrest due to chlorofluorocarbon inhalation.

Adult↗
PubMed1990

Stereoselective pharmacokinetics of 3,4-methylenedioxymethamphetamine in the rat.

Studies to characterize the pharmacokinetics of the enantiomers of MDMA were conducted in rats using the iliac arterial cannulation. Two routes of administration, intravenous and subcutaneous, were evaluated at two dose levels for each route [20 and 40 mg/kg (+/-)-MDMA for subcutaneous, 10 and 20 mg/kg (+/-)-MDMA for intravenous administrations]. The average half-life (+/- SD) for all dosing groups was 2.5 +/- 0.8 h for (-)-(R)-MDMA and 2.2 +/- 0.8 h for (+)-(S)-MDMA. The more rapid clearance of (+)-(S)-MDMA compared with (-)-(R)-MDMA is consistent with the area under the curve (AUC) data of the parent drug and its primary metabolite MDA. The mean (+/- SD) AUC S/R ratios of MDMA and MDA were 0.70 +/- 0.05 and 3.1 +/- 0.8, respectively. Following a 20 mg/kg dose of racemic MDMA iv the mean (+/- SD) of the percent dose excreted as (-)-(R)-MDMA, (+)-(S)-MDMA, (-)-(R)-MDA, and (+)-(S)-MDA were 20 +/- 10, 12 +/- 6, 3 +/- 1, and 6 +/- 2, respectively.

3,4-Methylenedioxyamphetamine↗
PubMed1990

Identification of metabolites of 3,4-methylenedioxymethamphetamine in rats.

Liquid chromatography with electrochemical detection (LC/ECD) and gas chromatography/mass spectrometry (GC/MS) were used to identify metabolites of N-methyl-3,4-methylenedioxyamphetamine (MDMA) in samples of rat plasma and urine. Several potential metabolites, based on what is known about the metabolism of the desmethyl analog (i.e., MDA), were synthesized as standards to aid in the identification of the MDMA metabolites. MDA and N-methyl-1-(4-hydroxy-3-methoxy-phenyl)-2-aminopropane (3b) were identified in urine by HPLC and confirmed by GC/MS. 1-(4-Hydroxy-3-methyoxyphenyl)2-aminopropane, (3a), N-methyl-1-(3-hydroxy-4-methoxyphenyl)-2-aminopropane (2b) and 1-(3,4-dihydroxyphenyl)-2-aminopropane (4a) were tentatively identified by LC/ECD but insufficient sample size precluded confirmation by mass spectrometry. MDA was also identified in brain and plasma extracts. Because MDA is a metabolite of MDMA in humans, and because it has been speculated that the neurotoxic effects of MDA and MDMA may be due to a metabolite, the results of the present study may ultimately aid our understanding of the neurotoxic mechanism of these drugs of abuse.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Determination of 3,4-methylenedioxyamphetamine and 3,4-methylenedioxymethamphetamine enantiomers in whole blood.

A method for the determination of the enantiomeric content of 3,4-methylenedioxyamphetamine (MDA) and 3,4-methylenedioxymethamphetamine (MDMA) in microsamples (200 microliters) of whole blood is described. The method involves liquid-liquid extraction of MDA and MDMA from blood and derivatization with the chiral reagent N-trifluoroacetyl-L-prolyl chloride. Separation, identification and quantitation of diastereomeric derivatives is by gas chromatography-mass spectrometry. The analytical range of the assay is from 0.12 ng to 48 ng injected on-column. Details for the synthesis of the enantiomers of MDMA are also provided.

3,4-Methylenedioxyamphetamine↗
PubMed1989

Stereochemistry of the metabolism of MDMA to MDA.

The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (LTPC) was used to form diastereomers of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) which were resolved on an achiral gas chromatographic column using a mass spectrometer as a detector. Rats were subcutaneously dosed with 40 mg/kg of (+/-) MDMA.HCl and blood was obtained by decapitation four hours after dosing. Plasma was separated and extracted. The extract was derivatized on-column with LTPC. In addition to the two MDMA isomers, the demethylated metabolites, S(+) and R(-)-MDA were identified. In all experimental groups (male rats, food deprived male rats, female rats, post partum female rats, and mice) dosed with racemic MDMA, higher levels of the S(+) isomer of MDA relative to the R(-) MDA isomer were observed. This may be significant since it has been shown that the S(+) isomer of MDMA is the more neurotoxic isomer of the racemic drug of abuse MDMA.

3,4-Methylenedioxyamphetamine↗
PubMedDate not supplied

Resolution of methamphetamine stereoisomers in urine drug testing: urinary excretion of R(-)-methamphetamine following use of nasal inhalers.

The objective of this study is to determine whether R(-)-methamphetamine inhaled from nasal inhalers produces positive methamphetamine results in currently used urine drug screening procedures and to present a rapid method for distinguishing the optical isomers of methamphetamine. Urine from three subjects inhaling from a Vicks Nasal Inhaler every 20 min for six hours tested positive for methamphetamine by EMIT, Toxilab, TDx, and GC/MS. The chiral derivatizing reagent N-trifluoroacetyl-L-prolyl chloride (L-TPC) was used to form methamphetamine diastereomers allowing rapid identification of each stereoisomer of methamphetamine present in the urine samples. Urine samples positive for amphetamines during routine drug screening were determined to consist of a racemic mixture of methamphetamine. The isomeric composition of methamphetamine present in a urine sample indicates the probable source of the drug.

Administration, Inhalation↗
PubMedDate not supplied

Improved CEDIA benzodiazepine assay eliminates sertraline crossreactivity.

Initial experiments demonstrated that the original CEDIA (cloned enzyme donor immunoassay) benzodiazepine assay crossreacted with setraline and sertraline metabolites. In response to this phenomenon, Boehringer Mannheim Corporation developed an improved CEDIA benzodiazepine assay in order to eliminate sertraline crossreactivity. The improved CEDIA assay was evaluated against the original CEDIA product, EMIT II (enzyme multiplied immunoassay technique) benzodiazepine assay, and electron capture negative chemical ionization (ECNCI) gas chromatography-mass spectrometry (GC-MS). Five hundred and thirty-one urine drug screens were tested by the immunoassays. Sensitivity and specificity of these immunoassays for the 5-aryl-7-chloro-1,4-benzodiazepine compounds were 92 and 98%, respectively, for the improved CEDIA assay; 92 and 93%, respectively, for the current CEDIA assay; and 87 and 98%, respectively, for EMIT II. The improved CEDIA assay performed almost identically to the EMIT II assay, both of which had a significant advantage over the original CEDIA product, which was subject to crossreactivity because of sertraline metabolites. The alpha-hydroxy ketone metabolites of sertraline are identified in human urine specimens for the first time using ECNCI GC-MS.

1-Naphthylamine↗
PubMedDate not supplied

CTCL in patients under 20 years of age: a series of five cases.

The diagnosis of cutaneous T-cell lymphoma in patients under 20 years of age is extremely rare. We report five patients diagnosed before 20 years of age who illustrate the striking variations in clinical and histologic features as well as disease progression. We feel this information stresses the importance of multiple biopsies in young patients with chronic dermatoses.

Adolescent↗