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A number of medical conditions are identified as risk factors for suicide death; in particular, cardiovascular illnesses are recognized as a major suicide risk factor. In this case, self-poisoning is the common method of suicide and cardiovascular drugs are among the major medications associated with fatal overdose, with calcium channel blockers being one of the most common agents. The present study describes two different fatal suicide cases involving four cardiovascular drugs: carvedilol, doxazosin and amlodipine (case 1) and diltiazem (case 2). The concentrations of the target cardiovascular drugs in the different biological specimens (central and femoral blood, urine, liver, brain) are presented, giving information about the potentially fatal data and the distribution of the drugs in the body. The study led to the implementation of a fast, sensitive and simple method for the detection and quantification of the four commonly prescribed cardiovascular drugs in post-mortem specimens including fluids and tissues for forensic purposes. The method was fully validated. The toxicological results of the studied cases are discussed, along with the autopsy results, histopathological evidence, and circumstances of death. The toxicological findings presented in the study provide new data regarding cardiovascular drugs in different post-mortem specimens, which will contribute to the currently limited knowledge about the toxicological profile of cardiovascular drugs and their distribution., Competing Interests: Declaration of Competing Interest The authors (A. L. Santunione, F. Palazzoli, P. Verri, D. Vandelli, V. Castagnetti, C. Profeta, E. Silingardi) declare that they do not have any financial or other relationships that might lead to a conflict of interest., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

New psychoactive substances (NPS) are substances that continue to appear on the drug market to bypass controlled substance legislation. Mephedrone or 4-methylmethcathinone is becoming the most popular new psychoactive substance among youth as a recreational drug. The present study describes the optimization and validation of a sensitive method that combined clean up procedure and LC-MS/MS technique designed to simultaneously determine the presence of Mephedrone and its two metabolites (normephedrone as active metabolite and dyhidromephedrone) in post-mortem specimens (body fluids and organ tissues). To date, this is the first determination of Mephedrone metabolites in post-mortem specimens. The validated method was applied to a fatal Mephedrone intoxication case. The distribution of the three analytes in different post-mortem matrices was presented. The toxicological results of the studied case are discussed, along with autopsy, histopathological evidence and crime-scene information. The toxicological results presented in the study provide new data relative to mephedrone and the distribution of its metabolites in post-mortem specimens. In our opinion, the metabolite concentration database must be developed because the metabolites may be linked to toxicity. The pattern of parent drug and its metabolites can be helpful in the interpretation of fatal cases involving mephedrone, which will contribute to the currently limited knowledge about mephedrone and metabolites concentrations., Competing Interests: Declaration of Competing Interest The authors report no declarations of interest., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Headache patients suffering from recurrent attacks are a population at risk of overuse and abuse of analgesic medications. Associated with triptans, the first-line drugs recommended for the acute treatment, these patients usually take other medications such as opioids analgesics for the attack treatment, antidepressants and antiepileptics for prophylaxis treatment and benzodiazepines, non-benzodiazepine hypnotics and antipsychotics for the treatment of comorbidities. Regular and frequent use of triptans, like of any other symptomatic analgesic, can cause chronic headache and medication-overuse headache (MOH). In these circumstances, a detoxification treatment is necessary and therefore the monitoring and follow-up of the patients are crucial to the success of the treatment. In the present study, a LC tandem MS method has been developed for the identification of 50 psychoactive drugs in human hair, including triptans, benzodiazepines and metabolites, analgesics, antiepileptic, antidepressants and metabolites, a non-benzodiazepine hypnotic (z-drug), antipsychotics and metabolites. Hair samples were decontaminated, pulverized and incubated overnight in methanol; the extracts were then purified by a new and rapid QuEChERS procedure and analyzed by LC-MS/MS under gradient elution with positive ionization MRM mode. The procedure was fully validated in terms of selectivity, linearity, limit of detection and lower limit of quantitation, precision and accuracy, carry-over, matrix effect, recovery and dilution integrity. The validated procedure has been applied to 234 real hair samples collected from headache patients with known type and dosage of the taken drugs; the obtained data could be of interest to evaluate the xenobiotic concentrations in patients with known therapy., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Butalbital, a barbiturate, is present in analgesic combinations used by headache sufferers. Overuse/abuse of these combinations may cause dependence, chronic migraine, and medication-overuse headache (MOH). MOH is difficult to manage: it improves interrupting analgesic overuse, but requires monitoring, because relapses are frequent. A gas chromatography-mass spectrometry (GC-MS) method for hair analysis has been developed and validated to document abuse of an analgesic combination containing butalbital and propyphenazone by a patient with MOH. For over ten years the patient managed her headache using eight suppositories/day of an analgesic combination containing butalbital 150mg, caffeine 75mg, and propyphenazone 375mg per suppository. An outpatient detoxification treatment was carried out. After three weeks, the patient reduced the consumption to one suppository/day. At the first control visit, after three months from the beginning of detoxification, the patient increased the use of the combination to four suppositories/day and at the second control visit, after seven months from the beginning of detoxification, she was back to eight suppositories/day. At the two control visits, a hair sample was taken for determination of butalbital and propyphenazone. Moreover blood and urine samples for determination of butalbital were drawn at the beginning of detoxification treatment and at the two control visits. With the segmental analysis of two hair samples the medication history of ten months could be estimated. In the first hair sample, collected at the first control visit, in the distal segment, butalbital and propyphenazone concentrations were, respectively, 17.5ng/mg and 56.0ng/mg, confirming the prolonged abuse; in the proximal segment, concurrently with the detoxification treatment, butalbital and propyphenazone concentrations had reduced respectively to 5.45ng/mg and 11.1ng/mg. The second hair sample, collected at the second control visit, proved the fair course of the detoxification treatment in the distal segment and signalled relapse in the abuse of the analgesic combination in the proximal segment. In the clinical context, hair analysis can be advantageously used to monitor the abuse of analgesic combinations with butalbital, common among headache patients. The validation data showed that GC-MS method developed for determination of butalbital and propyphenazone was rapid, highly sensitive, specific and selective., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Hair analysis, as complementary matrix, has expanded across the spectrum of toxicological investigations for misuse drug monitoring. Hair has become an important matrix for drug analysis, owing to the possibility to detect target analytes for long time periods, depending on hair length. A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method has been developed for the quantitation of tramadol, a widely used centrally acting analgesic, and its main metabolites in hair (ODMT, NDMT, NOT). Hair samples were decontaminated and incubated overnight in diluted hydrochloric acid; the extracts were purified by mixed-mode solid phase cartridges and analyzed by LC-MS/MS in positive ionization mode monitoring two transitions per analyte. The procedure was fully validated in terms of linearity, limit of detection and lower limit of quantitation (LLOQ), accuracy, precision, recovery, matrix effect and selectivity. The linear regression analysis was calibrated by deuterated internal standards; for all analytes, responses were linear over the range 0.04-40.00 ng/mg hair, with R(2) values of at least 0.995. The method offered satisfactory precision (RSD < 10%), accuracy (90-110%) and recovery (> 90%) values. The found LLOQ values for tramadol and metabolites were in the range 0.010-0.030 ng/mg hair. The proposed procedure was successfully applied to quantify tramadol and metabolites in real hair samples submitted to our laboratory: three cases of tramadol assumption within the therapeutic dosage (3 × 2 segments) and one case of tramadol abuse in a binge pattern (8 segments). The ranges found for TRAM, ODMT, NDMT and NOT were markedly higher in the abuse case (63.42-107.30, 3.76-6.26, 24.88-45.66, 0.22-1.18 ng/mg hair, respectively) compared to the other case reports (3.29-20.12, 0.28-1.87, 0.45-4.32, 0.07-0.80 ng/mg, respectively); also the values of NMDT/ODMT ratio differed significantly. According to the obtained data, we hypothesized that the binge pattern may influence the metabolites' to parent drug concentration ratios; therefore this parameter could represent a target assessment tool to monitor abuse cases., (Copyright © 2014 Elsevier B.V. All rights reserved.)