Suspected Overdose Cases Research Articles

Toxicological Analysis of Fluorofentanyl Isomers in Postmortem Blood.

The opioid epidemic continues to evolve in the USA, with fentanyl the most prevalent synthetic opioid in fatal drug overdoses. Following the scheduling of fentanyl's core structure in 2018, there was a notable decline in the prevalence of fentanyl analogs in decedents; however, fluorofentanyl began being reported in casework in the winter of 2020. Fluorofentanyl has three positional isomers (para-fluorofentanyl (p-FF), ortho-fluorofentanyl (o-FF) and meta-fluorofentanyl (m-FF)), with the most predominant isomer that has recently emerged in the USA being p-FF. The goal of this study was to identify p-FF in postmortem cases between October 2020 and April 2021. Urine and blood were extracted using UCT Clean Screen® extraction columns and then screened using an Agilent 1290 Infinity liquid chromatograph (LC) coupled to an Agilent 6545 accurate mass time-of-flight mass spectrometer (TOF-MS) and quantified using an Agilent 6890N GC system coupled with an Agilent 5973 MS. The limit of quantitation (LOQ) for fentanyl, acetyl fentanyl, butyryl fentanyl, p-FF, o-FF and m-FF was 2.5 ng/mL. The screening method could not differentiate the three positional isomers of fluorofentanyl. Suspected overdose cases (n = 370) received from October 2020 through April 2021 from four Medical Examiner Districts in the state of Florida were analyzed for the presence of fluorofentanyl. The LC-QTOF-MS screen yielded 27 decedents positive for fluorofentanyl, with a majority being Caucasian (93%) and male (70%) with ages ranging from 27 to 63 years. Analysis of the blood and urine by GC-MS yielded 14 decedents positive for p-FF, nine of which were positive in the blood. The blood concentrations (n = 9) for p-FF ranged from <LOQ to 30 ng/mL, with an average and median of 9.9 ng/mL and 5.5 ng/mL, respectively. p-FF was identified in the blood of 33% of the cases, and the concentration of p-FF was generally higher than previously reported.

LC-MS/MS method for rapid and accurate detection of caffeine in a suspected overdose case

Excessive intake of caffeine, otherwise known to be a safe and mild central nervous system stimulant, causes nausea, vomiting, convulsions, tachycardia, and eventually fatal arrhythmias and death. Caffeine intoxication, a global problem, has been increasing in Japan since 2013. Thus, there is a need for rapid and accurate diagnosis of caffeine poisoning in forensic and clinical toxicology investigations. Herein, we demonstrate rapid and accurate caffeine quantitation by liquid chromatography tandem mass spectrometry using the standard addition method in a fatal case. Biological samples were diluted 500–100,000-fold and subjected to a simple pretreatment (adding caffeine standard and internal standard and passing through a lipid removal cartridge). The multiple reaction monitoring transitions were 195 → 138 for quantitation, 195 → 110 for the qualifier ion, and 204 → 144 for the internal standard (caffeine-d9). The standard plots were linear over 0–900 ng/mL (r2 = 0.9994–0.9999) for biological samples, and the reproducibility (%RSD) of the method was 1.53–6.97% (intraday) and 1.59–10.4% (interday). Fatal levels of caffeine (332 μg/mL) and toxic to fatal levels of olanzapine (625 ng/mL), along with other pharmaceuticals were detected in the external iliac venous blood. The cause of death was determined to be multi-drug poisoning, predominantly caused by caffeine. Our method is useful for not only forensic cases but also the rapid diagnosis of caffeine overdose in emergency clinical settings.

Development and validation of an analytical method for quantification of 15 non-tricyclic antidepressants in serum with UPLC-MS/MS

Non-tricyclic antidepressants are often encountered in overdose cases, and for some of them therapeutic monitoring might be warranted. Therefore, we developed and validated an ultra-performance liquid chromatography-tandem mass spectrometry method for the quantification of 15 common non-tricyclic antidepressants in serum: citalopram, desmethylcitalopram, desmethylfluoxetine, desmethylvenlafaxine, duloxetine, fluoxetine, fluvoxamine, melitracen, mianserin, mirtazapine, paroxetine, reboxetine, sertraline, trazodone and venlafaxine. The selected pharmaceuticals represent the most common non-tricyclic antidepressants available in Belgium. Serum samples (250 μL) were precipitated with methanol and acetonitrile containing 5 ng of the internal standards: mirtazapine-D 4 , paroxetine-D 5 , reboxetine-D 6 and venlafaxine-D 6 . The supernatant was evaporated at 56 °C under a flow of nitrogen and reconstituted in 100 μL of 50:50 methanol:water with 2 mM ammonium acetate. Five μL were injected and the target analytes were separated on a 100 × 2.1 mm ACQUITY BEH C18 column (Waters, Zellik, Belgium) using a Waters ACQUITY Ultra-Performance Liquid Chromatography system. The analytes were eluted within 7.5 min, using a gradient of 2 mM ammonium acetate and 0.1% formic acid in water and in methanol at a flow rate of 0.4 mL/min. Quantification was performed on a Waters triple-quadrupole ACQUITY TQD using multiple reaction monitoring (MRM) in positive mode (2 MRMs per analyte). A six-point calibration curve was used to cover a large concentration range from 10 ng/mL to 1000 ng/mL. The developed method was validated in terms of selectivity, linearity, precision, accuracy, matrix effect, recovery and stability. No interfering signals from matrix, internal standard or tricyclic antidepressant drugs were found. Limits of quantification and limits of detection ranged from 10 to 85 ng/mL and 2.0 to 28 ng/mL respectively. Ion suppression from matrix effects varied from 36 to 108% for the compounds and 47 to 102% for the internal standards. Process efficiency varied from 22 to 106%. Intra- and interassay precision varied from 87.7 to 96.5% and 87.7 to 96.9%, respectively. The bias of the assay was lower than 15% for all the compounds, except the lowest concentrations of desmethylcitalopram and trazodone (bias < 20%). Good validation performance was obtained thanks to the use of selected deuterated internal standards that adjusted for all of the compounds. This method is therefore suitable for quantification in suspected overdose cases and can be use in a clinical Toxicology lab in a daily basis.

Resuscitation characteristics and outcomes in suspected drug overdose-related out-of-hospital cardiac arrest

IntroductionWe sought to compare characteristics of emergency medical services-treated out-of-hospital cardiac arrests resulting from suspected drug overdose with non-overdose cases and test the relationship between suspected overdose and survival to hospital discharge. MethodsData from emergency medical services-treated, non-traumatic out-of-hospital cardiac arrests from 2006 to 2008 and late 2009 to 2011 were obtained from four EMS agencies in the Pittsburgh, Pennsylvania metropolitan area. Case definition for suspected drug overdose was naloxone administration, indication on the patient care report and/or indication by a review of hospital records. Resuscitation parameters included chest compression fraction, rate, and depth and the administration of resuscitation drugs. Demographic and outcome variables compared by suspected overdose status included age, sex, and survival to hospital discharge. ResultsFrom 2342 treated out-of-hospital cardiac arrests, 180 were suspected overdose cases (7.7%) and were compared to 2162 non-overdose cases. Suspected overdose cases were significantly younger (45 vs. 65, p<0.001), less likely to be witnessed by a bystander (29% vs. 41%, p<0.005), and had a higher rate of survival to hospital discharge (19% vs. 12%, p=0.014) than non-overdoses. Suspected overdose cases had a higher overall chest compression fraction (0.69 vs. 0.67, p=0.018) and higher probability of adrenaline, sodium bicarbonate, and atropine administration (p<0.001). Suspected overdose status was predictive of survival to hospital discharge when controlling for other variables (p<0.001). ConclusionPatients with suspected overdose-related out-of-hospital cardiac arrest were younger, received different resuscitative care, and survived more often than non-overdose cases.

Blood, Brain, and Hair GHB Concentrations Following Fatal Ingestion

Despite the increasing incidence of illicit use of gamma-hydroxybutyrate (GHB), little information is available documenting levels of the drug in GHB fatalities. We measured GHB levels in postmortem blood, brain and hair specimens from a suspected overdose case by gas chromatography/mass spectrometry (GC/MS) following solid phase extraction (SPE) and derivatization with bis(trimethyl-silyl) trifluoroacetamide (BSTFA). Examination found 330 microg/mL GHB in femoral blood and 221 ng/mg GHB in frontal cortex brain tissue, values higher than those typically reported in the literature. The hair shaft was negative for GHB whereas the plucked root bulbs with outer root sheath attached (2,221 ng/mg) and root bulbs after washing and removal of the outer root sheath (47 ng/mg) contained the drug. Our results are consistent with an acute single dose of GHB and, as the toxicology screen was negative for other drugs of abuse, emphasize the significant danger of this drug.

Diagnosis and treatment of acute fluoride toxicity

The literature has shown overwhelmingly that fluoride used for dental prophylaxis presents minimal risks if used appropriately. However, there is an increasing potential for ingestion of toxic doses of fluoride because of the increasing use of pleasant-tasting fluoride products. The ADA has recommended that no more than 120 mg fluoride (264 mg NaF) be dispensed at any one time. As with any medication, fluoride preparations should be prescribed in child-resistant containers, and patients or parents (or both) should be instructed as to the proper daily treatment regimens and the potential for toxic overdoses. Possibly the greatest risk of fluoride intoxication relates to the concentrated fluoride preparations used for professionally applied fluoride treatment (Table 3). Therefore, patients receiving professional topical fluoride treatments should have well-fitting trays with the minimal amount of fluoride necessary to contact the teeth. These patients should be provided with a saliva ejection system, and they should never be left unobserved during the topical application. Health professionals should be aware of the potential toxic effects of fluoride in addition to the well-known caries preventive effects. It is necessary to know how to calculate the amount of fluoride ingested and the emergency treatment recommended to prevent toxic effects in suspected overdose cases.

Quantitative Gas Chromatographic Determination of Acetaminophen Using Trimethylanilinium Hydroxide as the Derivatizing Agent

Abstract Pharmaceutical preparations of acetaminophen, an analgesic, are marketed and extensively used in the single drug form such as Tylenol® and Datril® and in combination with other analgesics such as aspirin and salicylamide in Excedrin® Excedrin P.M.® and others. Acetaminophen overdosage can result in centrilobular hepatic necrosis or hepatic failure [1] with severe overdosage resulting in a high fatality rate [2]. Workers have investigated and related severity of liver damage to drug serum concentration [1,3, 4]. Initial concentrations relative to time of ingestion and drug half-life are two criteria in the early diagnosis of possible liver damage or necrosis [4]. Administration of cysteamine soon after ingestion has been advocated [3] after successful use in severe overdosages, but its use is a risk to the patient and warranted only in cases of probable severe or fatal hepatic necrosis. Consequently, for intelligent therapy of suspected overdose cases and legal protection of physicians, rapid and accurate serum acetaminophen levels must be available throughout the first few critical hours after ingestion of acetaminophen.

Initial experience with a toxicology screening programme

A scheme for drug identification in overdosed patients has been developed, using a combination of the techniques of extraction, thin layer and gas chromatography, ultra violet spectroscopy and colorimetry. 5 ml plasma and 50 ml urine or gastric aspirate is required for the full drug screen, which can be completed within 2 h. Fifty-three drugs are presently encompassed by the screen, and include analgesics, alcohols, antihistamines, anticonvulsants, barbiturates and related compounds, narcotics, phenothiazines, sedatives, tranquillizers and tricyclic antidepressants. 37% of analyses on 74 suspected overdose cases confirmed a provisional diagnosis and a further 47% clarified a general ‘drug overdose’ diagnosis. In 4 patients the results conflicted with the provisional diagnosis. Barbiturates were detected in 28% of the positive results and sedatives, tranquillizers or antidepressants in 39%. Analgesics accounted for a further 13% of the positive overdose screens. Many patients were found to have taken mixtures of drugs.