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Biomedical subjects

A Poklis

Publications and source records attributed to A Poklis.

At least 37 records · Page 2Linked to original sources
PubMed1997

Fatal fentanyl intoxication following excessive transdermal application.

The case history and toxicological findings of a fatal fentanyl intoxication due to the application of multiple transdermal patches are presented. An 83 year-old white female with terminal cancer was found dead with three 100 mg/h fentanyl patches on her chest. The autopsy and subsequent histological studies revealed extensive areas of gastric carcinoma, a large atrial tumor, ulceration of esophagus, metastasis of peripancreatic lymph nodes and a recent surgical removal of part of the lower lobe of the left lung. Toxicological analysis by GC/MS yielded fentanyl concentrations of blood, 25 ng/mL; brain, 54 ng/g; heart 94 ng/g; kidney 69 ng/g; and liver 104 ng/g. The cause of death was determined to be fentanyl overdose and the manner of death was ruled undetermined as the investigation was unable to conclusively establish whether this was an accidental overdose, a suicide, an assisted suicide, or possible a homicide. This case demonstrates the need for caution in self-administration of transdermal fentanyl patches, in particular, the dangers inherent in the application of multiple patches which can result in the release of potentially toxic or lethal doses.

Administration, Cutaneous↗
PubMed1996

Distribution of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) stereoisomers in a fatal poisoning.

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.

3,4-Methylenedioxyamphetamine↗
PubMed1996

Gas chromatographic procedures for determination of ethanol in postmortem blood using t-butanol and methyl ethyl ketone as internal standards.

Three gas chromatographic procedures for the determination of ethanol in postmortem blood using alternative internal standards to n-propanol are presented: a direct injection procedure using t-butanol, and two headspace methods using t-butanol and methyl ethyl ketone. t-Butanol and methyl ethyl ketone were well resolved from ethanol, acetone, methanol and other commonly observed putrefactive volatiles using direct injection or headspace analysis. CVs for the direct injection method were below 5% for ethanol and below 10% for the other volatiles. The lower limits of detection (LOD) were 25-50 mg/L. The CVs for the headspace methods were below 5% for ethanol and below 6% for the other volatiles. The LODs were 10 mg/L using either t-butanol or methyl ethyl ketone as internal standards. The use of t-butanol or methyl ethyl ketone as alternatives to n-propanol avoids the possibility of error in the quantitation of ethanol due to the presence of n-propanol and allows for the identification of other volatiles that may aid in distinguishing antemortem ingestion from postmortem production of ethanol.

Butanols↗
PubMed1996

Pharmacological characterization of BNMPA (alpha-benzyl-N-methylphenethylamine), an impurity of illicit methamphetamine synthesis.

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, has previously been reported to produce convulsions in mice without affecting spontaneous locomotor activity or altering methamphetamine-induced increases in spontaneous activity. In this study the in vitro effects of BNMPA on a variety of neuronal receptor types was determined to better characterize the pharmacological actions of this novel compound. BNMPA and N-demethyl-BNMPA fully displaced the dopamine transporter selective ligand [3H]CFT (2-beta-carbomethoxy-3-beta-(4-fluorophenyl)tropane) from rat striatal membranes with Ki values (mean +/- S.E.M) of 6.05 microM +/- 0.15 and 8.73 microM +/- 1.66, respectively. BNMPA also inhibited [3H]dopamine uptake into striatal synaptosomes with an IC50 value of 5.1 +/- 1.4 microM. The basal efflux of [3H]dopamine from striatal slices was slightly enhanced by BNMPA only at concentrations > or = 100 microM. BNMPA had no effect on [3H]norepinephrine efflux from hippocampal slices. BNMPA displaced tritiated paroxetine and prazosin binding from rat cortical membranes with Ki values of 14.5 microM and 11.7 microM respectively. In electrophysiological studies, BNMPA (100 microM) had no significant effects on either GABAA Cl- currents in cultured neurons or non-NMDA glutamate receptors expressed in oocytes. However, BNMPA significantly inhibited NMDA-stimulated currents in oocytes expressing the NR1/2A or NR1/2C receptor subunit combinations (IC50 values = 24.6 +/- 1.8 and 24.0 +/- 1.5 microM, respectively). This inhibition was rapid, reversible and voltage-dependent. These results indicate that BNMPA has multiple sites of action in the CNS that could be important in modulating a variety of behavioral effects upon exposure to this synthetic byproduct of illicit methamphetamine synthesis.

Analysis of Variance↗
PubMed1996

Determination of gabapentin in serum using solid-phase extraction and gas-liquid chromatography.

A gas-liquid chromatographic method for the determination of gabapentin (Neurontin) is described. The method involves extracting 0.5 mL of acidified sample by C18 solid-phase column, derivatization with MTBSTFA plus 1% tBDMCS, and analysis on an HP-1 column with a flame-ionization detector. Quantitation was performed with peak-height ratios of gabapentin to a gabapentin analogue [(1-aminomethyl-1-cycloheptyl) acetic acid] as the internal standard. The assay had a limit of detection of 0.2 mg/L and a linear range from 0.5 to 30.0 mg/L. Several compounds were analyzed for potential interference, and none interfered with the assay.

Acetamides↗
PubMed1996

Postmortem production of ethanol and factors that influence interpretation: a critical review.

Ethanol analysis is the most frequently performed assay in forensic toxicology laboratories. Interpretation of postmortem ethanol findings are often confounded by postmortem production of ethanol. Many species of bacteria, yeast, and molds are capable of producing ethanol from a variety of substrates. The probability of postmortem ethanol synthesis increases as storage temperature and the interval between death and autopsy increases. It is often difficult to distinguish between postmortem ethanol production and antemortem alcohol ingestion. This review presents a discussion of the criteria for the identification of postmortem ethanol synthesis and factors to consider in the interpretation of postmortem ethanol findings. The criteria include case history, condition of the specimens, types of microbes present, atypical fluid and tissue distribution of ethanol, the concentration of ethanol present, and the detection of other alcohols and volatiles. With careful consideration of all the information available, a valid interpretation of the source of ethanol, whether it be from antemortem ingestion or postmortem production, can be made.

Ethanol↗
PubMed1996

The detection of a metabolite of alpha-benzyl-N-methylphenethylamine synthesis in a mixed drug fatality involving methamphetamine.

A 37-year-old, white male collapsed at his home following a party. He reportedly had a history of unspecified cardiac arrhythmia. The ambulance crew found him unresponsive and an ECG revealed ventricular tachycardia/fibrillation. Following one hour of resuscitative efforts in the ambulance and emergency room of a local hospital, he was pronounced dead. An antemortem urine toxicology screen performed at the hospital was "positive" for benzodiazepines, cocaine and amphetamine/methamphetamine. At autopsy, there was generalized organ congestion with no evidence of trauma or other significant pathology except mild, left ventricular hypertrophy. Quantitation by gas chromatography/mass spectrometry (GC/MS) of methamphetamine in bile, blood, urine and gastric contents yielded 21.7, 0.7, 32.0 and 2.9 mg/L, respectively. Liver and brain contained 2.2 and 2.7 mg/kg, respectively. A trace amount of p-OH-alpha-benzyl-N-methylphenethylamine (p-OH-BNMPA), a metabolite of alpha-benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis, was also detected in the urine. Since these impurities can be characteristic of a particular synthetic method, their presence in seized samples or their detection in biological samples from methamphetamine users can further be used to monitor the sales of precursor chemicals, group seized compounds to common sources of illicit production or provide links between manufacturers, dealers and users.

Adult↗
PubMed1995

Fatal morphine poisoning in a child due to accidental oral ingestion.

A case of fatal intoxication of an 8 year old child due to accidental oral ingestion of morphine is presented. Following a tonsillectomy and release from the hospital the decedent was prescribed meperidine syrup 50 mg per teaspoon (tsp) to be taken 2 tsps every 4 h. A pharmacist when filling her prescription mistakenly dispensed Roxanol which contained 20 mg/ml morphine sulfate. She took 1 or 2 tsp of the prescription prior to bed and was found dead the next morning. Autopsy findings were unremarkable. Quantitation by gas chromatography/mass spectrometry (GC/MS) yielded the following morphine results: blood, 0.128 mg/l; bile, 135 mg/l and stomach contents, 16 mg/l (2.3 mg total). Based upon the clinical history, autopsy and toxicology finding the cause of death was determined to be poisoning by morphine and the manner of death accidental.

Administration, Oral↗
PubMed1995

alpha-Benzyl-N-methylphenethylamine (BNMPA), an impurity of illicit methamphetamine synthesis: pharmacological evaluation and interaction with methamphetamine.

Methamphetamine is a popular drug of abuse, readily synthesized in clandestine laboratories. Illicitly obtained methamphetamine is frequently impure, containing various purposefully added diluents and adulterants, as well as impurities of manufacture and origin. Few impurities have been studied in vivo and limited information exists concerning their pharmacology/toxicology. One such impurity of manufacture is alpha-benzyl-N-methylphenethylamine (BNMPA). Acute toxicity and spontaneous activity (locomotor) studies were conducted with this compound alone and in combination with S(+)-methamphetamine (METH) in male, ICR mice. In the acute toxicity studies, BNMPA was evaluated for convulsant activity. While BNMPA also produced some behavioral disturbances similar to those seen with methamphetamine (e.g., stereotopy) at doses greater than 30 mg/kg, no tonic-clonic convulsions were noted until pre-terminal convulsion at 50 mg/kg. METH alone produced tonic-clonic convulsions at terminal doses of 70 mg/kg. When BNMPA was given in combination with METH, there was no readily apparent change in the convulsion profile from that of METH given alone. In spontaneous activity studies, doses of BNMPA ranging from 1 mg/kg to 50mg/kg failed to alter locomotor activity significantly from controls though 5 mg/kg METH alone significantly increased spontaneous activity. In addition, increases in spontaneous activity elicited by 5 mg/kg METH were not affected when METH was given with 5 mg/kg BNMPA. While BNMPA appears to have toxic effects in the central nervous system (CNS), the failure to affect locomotor activity or alter either METH-induced increases in spontaneous activity or METH-induced convulsions suggests that the two agents are producing their effects through distinct mechanisms.

Animals↗
PubMed1995

Chromatographic procedures for the determination of felbamate in serum.

A gas-liquid chromatographic procedure and a high-performance liquid chromatographic (HPLC) procedure for the quantitative determination of the anticonvulsant drug felbamate in serum are presented. Both methods employ methyl felbamate as the internal standard. The efficiencies of felbamate extraction by both C18 solid-phase extraction (SPE) followed by HPLC and liquid-liquid extraction followed by gas chromatography (GC) were evaluated. The mean absolute recovery of felbamate over a serum concentration range of 10-100 mg/L for SPE and liquid-liquid extraction were 89.4 and 84.4%, respectively. Calibration curves for the GC and HPLC procedures were linear from 5 to 200 mg/L felbamate. The overall within-run precision of liquid-liquid extraction followed by GC analysis yielded coefficients of variation Os) of 7.3% at 16 mg/L (n = 10) and 5.8% at 100 mg/L (n = 10). The overall between-run precision for this method calculated by three determinations on a single day for three successive weeks yielded CVs of 7.8% at 16 mg/L (n = 45) and 6.3% at 100 mg/L (n = IO). The overall within-run precision of SPE followed by HPLC analysis yielded a CV of 2.9 % at 50 mg/L (n = 10), and the overall between-run precision for this method calculated by three determinations on a single day for three successive weeks yielded CVs of 3.3% at 25 mg/L (n = 40) and 3.5% at 50 mg/L (n = 37). The SPE-HPLC procedure was found to yield less variable results than the liquid-liquid-GC procedure. Limits of quantitation and detection of both methods were set at 5 mg/L felbamate. Popular anticonvulsant and acid or neutral extractable drugs did not interfere with either the GC or HPLC methods. The results of an interlaboratory, intermethod comparison study performed on patient serum specimens analyzed in one laboratory by the SPE-HPLC procedure and in another laboratory by the liquid-liquid extraction-GC procedure correlated well (r2 = 0.967; n = 41). Both methods provide clinically useful and comparable results.

Administration, Oral↗
PubMed1995

Response of EMIT amphetamine immunoassays to urinary desoxyephedrine following Vicks inhaler use.

The cross-reactivity of l-methamphetamine (l-desoxyephedrine) to the EMIT-d.a.u. class (EC) and EMIT-d.a.u. monoclonal amphetamine/methamphetamine (EM) assays was evaluated in urine specimens collected from six subjects using Vicks inhalers. The subjects were five men and a woman ranging from 27 to 47 years old. Four subjects used the inhaler as recommended by the manufacturer for five consecutive days; two subjects used double this dosage for three consecutive days. All urine voids were collected, totaling 132 specimens. All specimens were analyzed by the EC and EM assays. Specimens yielding a positive response were then analyzed by chiral and achiral gas chromatography/mass spectrometry (GC/MS). No specimen was positive by the EM assay, whereas 17 specimens yielded positive EC results. One subject for form the "as recommended" group had six positive specimens with maximum l-desoxyephedrine of 872 ng/ml. Both subjects using twice the recommended dosage had positive specimens, maximum l-desoxyephedrine of 1,560 ng/ml. No positive specimen contained > 200 ng/ml l-amphetamine.

Administration, Inhalation↗
PubMed1995

Fentanyl: a review for clinical and analytical toxicologists.

Fentanyl is a highly potent, short acting synthetic analgesic indicated as a preanesthetic medication. It is available for intravenous injection, as a transdermal patch and a lozenge dosage form. Fentanyl displays a large apparent volume of distribution, short plasma half life and extensive biotransformation. It is a popular drug of abuse among health care professionals. Diversion of pharmaceutical fentanyl preparations, as well as the availability of illicitly synthesized potent and highly toxic fentanyl analogs have resulted in numerous overdose deaths. Analysis of fentanyl and fentanyl analogs requires highly selective and sensitive methodologies. This review is intended as a quick reference source for clinical and analytical toxicologists.

Animals↗
PubMed1995

Stereoselectivity of the TDxADx/FLx Amphetamine/Methamphetamine II amphetamine/methamphetamine immunoassay--response of urine specimens following nasal inhaler use.

The TDxADx/FLx Amphetamine/Methamphetamine II fluorescence polarization immunoassay (Abbott Diagnostic) for the detection of amphetamine and methamphetamine in urine was evaluated for stereoselectivity and response to specimens collected following as recommended and double the recommended dose use of Vicks Nasal Inhaler. The assay is calibrated with d-amphetamine, at cutoff concentration of 300 ng/mL for a positive response. Cross-reactivity studies demonstrated a positive result with 1000 ng/mL l-amphetamine, 300 ng/mL d-methamphetamine, and approximately 2000 ng/mL desoxyephedrine. A good correlation was observed between urines obtained following ingestion of d-amphetamine simultaneously analyzed by TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry: r2 = 0.954, N = 100. However, urine obtained following ingestion of racemic methamphetamine showed no correlation between TDxADx/FLx Amphetamine/Methamphetamine II and gas chromatography/mass spectrometry results: r2 = 0.420, N = 28. Urines collected following as recommended use for five consecutive days of Vicks Nasal Inhaler containing l-desoxyephedrine did not yield positive TDxADx/FLx Amphetamine/Methamphetamine II results. Only two urines from a subject using twice the recommended inhaler dose yielded positive TDxADx/FLx Amphetamine/Methamphetamine II results. These urines contained 1560 and 1530 ng/mL desoxyephedrine when analyzed by gas chromatography/mass spectrometry. Greater than recommended use of Vicks Nasal Inhaler may yield false positive TDxADx/FLx Amphetamine/Methamphetamine II results for amphetamine use when calibrated at 300 ng/mL d-amphetamine. If calibrated at 1000 ng/mL, d-amphetamine, the TDxADx/FLx Amphetamine/Methamphetamine II is unlikely to yield false positive results for amphetamine, even following excessive inhaler use.

Adult↗
PubMed1994

Thioridazine enantiomers in human tissues.

Enantiomers of thioridazine (TRZ) were determined in postmortem tissues obtained from a patient on chronic TRZ therapy by sequential achiral and chiral high pressure liquid chromatography. Tissue concentrations of (+)-TRZ found in liver, brain, bile and blood were: 6.46, 0.40, 0.48 and 0.07 mg/l or mg/kg, respectively. Concentrations of (-)-TRZ in liver, brain, bile and blood were: 12.2, 0.81, 1.07 and 0.20 mg/l or mg/kg, respectively. These data demonstrate the stereoselective disposition of TRZ in human tissues.

Adult↗
PubMed1994

Detection of benzodiazepines and tribenzazolams by TRIAGE: confirmation by solid-phase extraction utilizing SPEC.3ML.MP3 microcolumns and GC-MS.

A new point-of-care urine drugs-of-abuse testing device, the BIOSITE TRIAGE, was evaluated for detection of benzodiazepines (BNZs). TRIAGE utilizes a unique, competitive, visual immunoassay methodology to simultaneously detect seven classes of drugs of abuse. Because of the unique ASCEND Multimmunoassay technology, conflicting results may arise when TRIAGE is compared with conventional immunoassay techniques. Apparent TRIAGE BNZ false-positive results may occur when gas chromatographic-mass spectrometric (GC-MS) confirmation utilizes oxazepam as the analyte used to confirm the presence of BNZs. TRIAGE BNZ results were correlated with those of Syva EMIT, (n = 106, overall agreement 85%). Both negative and positive urine samples were tested by GC-MS for the following drugs: oxazepam, nordiazepam, desalkylflurazepam, OH-ethylflurazepam, lorazepam, temazepam, alpha-OH-alprazolam and alpha-OH-triazolam. Urine samples were extracted using the new ANSYS SPEC.3ML.MP3 solid-phase extraction microcolumn. The ANSYS procedure for BNZs was modified to include desalkylflurazepam, OH-ethylflurazepam, lorazepam, temazepam, alpha-OH-alprazolam, and alpha-OH-triazolam. Deuterated oxazepam and alpha-OH-alprazolam were used as internal standards. Limits of quantitation (LOQs) ranged from 25 to 100 ng/mL with a limit of detection of 25 ng/mL for all analytes. Individual analytes demonstrated within-run precision and between-run precision ranging from 0.9 to 4.7% CV and 1.3 to 16.9% CV, respectively. All analytes were linear from their LOQs to 1000 ng/mL.

Benzodiazepines↗