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1.
Toxicon ; 187: 122-128, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32891666

RESUMO

Direct analysis in real time (DART) coupled to high-resolution mass spectrometry (HRMS) was applied for the first time to veterinary forensic toxicology to investigate the presence of toxic compounds in hay after an episode of acute intoxication in a dairy cattle farm. In addition to gross field necropsy and histological examination, microbial cultures, and heavy metals analysis, the molecular fingerprinting of the suspected hay batch was investigated by DART-HRMS. DART-HRMS revealed a distinct signal of m/z 507.2289 in the hay batch thought to be associated with the digestive complications. A search on chemical structure databases matched the ion with asperphenamate, a toxin produced by Penicillium spp. and Aspergillus spp. Liquid Chromatography-HMRS analysis and electrospray-HRMS-MS/MS of the hay extracts further characterized the structure and confirmed the identification of the compound as asperphenamate. Asperphenamate is fungal metabolite which can have cytotoxic and antitumor activity in humans, and it is classified as acute toxicant and harmful if swallowed.


Assuntos
Doenças dos Bovinos/diagnóstico , Constipação Intestinal/veterinária , Fenilalanina/análogos & derivados , Animais , Aspergillus , Bovinos , Constipação Intestinal/complicações , Constipação Intestinal/diagnóstico , Toxicologia Forense , Fenilalanina/análise , Espectrometria de Massas em Tandem
2.
Artigo em Chinês | MEDLINE | ID: mdl-32746581

RESUMO

From August 21 to December 13, 2018, a tetramine poisoning incident in Wenzhou, Zhejiang Province was investigated, and the clinical diagnosis and treatment of tetramine poisoning was analyzed. There were 6 cases of poisoning caused by artificial tetramine poisoning. The diagnosis was delayed, coma and convulsions were severe manifestations continuous renal replacement therapy (CRRT) was effective in the treatment of severe cases, and all 6 cases were cured. The possibility of poisoning should be considered for unexplained coma and/or convulsions. Although tetramine is banned, it still needs to be highly vigilant and avoids the recurrence of delayed diagnosis and treatment.


Assuntos
Hidrocarbonetos Aromáticos com Pontes/envenenamento , Envenenamento/diagnóstico , Acidentes , Coma , Toxicologia Forense , Humanos , Envenenamento/terapia , Convulsões/induzido quimicamente
3.
J Anal Toxicol ; 44(7): 637-650, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32754738

RESUMO

The endogenous presence of gamma-hydroxybutyric acid (GHB) complicates the interpretation of results in cases where an exogenous dosing is suspected. Due to GHB's rapid metabolism and clearance following exogenous doses, hair has become a preferential matrix for confirmation of GHB exposure in drug-facilitated crimes. However, unlike blood and urine where an agreed-upon cut-off concentration for differentiation between endogenous and exogenous GHB has been made, there has been no consensus on a cut-off concentration for hair. This is due in part to the wide inter- and intra-individual variation that has been observed in endogenous GHB hair studies. A large (>50) population study of 214 donors was conducted to better understand these variations and to evaluate whether a cut-off concentration could be established for endogenous GHB in human hair. As seen in our previous study, the inter-individual variation was large, with concentrations ranging from <0.40 to 5.47 ng/mg. This range made an absolute cut-off concentration recommendation inappropriate, so an alternative approach for GHB discrimination was investigated utilizing the intra-individual variation. Male donors appeared to have greater intra-individual variation than female donors, yet it was noted that segment-to-segment variation along the length of hair had minimal change between individual donor's adjacent segments. Overall, 97.1% of the adjacent segment differences were within ±0.5 ng/mg. Therefore, instead of a recommended cut-off concentration, it appears that using adjacent segment concentration differences could be a strategy to assist in differentiating endogenous from single exogenous GHB exposure. In the absence of controlled dosing data, previously published segmented results from controlled and suspected dosing donors are examined using the adjacent segmental difference approach and the results compared to currently used ratio-based calculations.


Assuntos
Cabelo/química , Hidroxibutiratos/análise , Feminino , Toxicologia Forense , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Masculino
4.
J Anal Toxicol ; 44(7): 708-717, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32808043

RESUMO

An analytical method for the detection of 40 benzodiazepines, (±)-zopiclone, zaleplon and zolpidem in blood and urine by solid-phase extraction liquid chromatography-tandem mass spectrometry was developed and validated. Twenty-nine of 43 analytes were quantified in 0.5 mL whole blood for investigating postmortem, drug-facilitated sexual assault (DFSA) and driving under the influence of drugs cases (DUID). The four different dynamic ranges of the seven-point, linear, 1/x weighted calibration curves with lower limits of quantification of 2, 5, 10 and 20 µg/L across the analytes encompassed the majority of our casework encountered in postmortem, DFSA and DUID samples. Reference materials were available for all analytes except α-hydroxyflualprazolam, a hydroxylated metabolite of flualprazolam. The fragmentation of α-hydroxyflualprazolam was predicted from the fragmentation pattern of α-hydroxyalprazolam, and the appropriate transitions were added to the method to enable monitoring for this analyte. Urine samples were hydrolyzed at 55°C for 30 min with a genetically modified ß-glucuronidase enzyme, which resulted in >95% efficiency measured by oxazepam glucuronide. Extensive sample preparation included combining osmotic lysing and protein precipitation with methanol/acetonitrile mixture followed by freezing and centrifugation resulted in exceptionally high signal-to-noise ratios. Bias and between-and within-day imprecision for quality controls (QCs) were all within ±15%, except for clonazolam and etizolam that were within ±20%. All 29 of the 43 analytes tested for QC performance met quantitative reporting criteria within the dynamic ranges of the calibration curves, and 14 analytes, present only in the calibrator solution, were qualitatively reported. Twenty-five analytes met all quantitative reporting criteria including dilution integrity. The ability to analyze quantitative blood and qualitative urine samples in the same batch is one of the most useful elements of this procedure. This sensitive, specific and robust analytical method was routinely employed in the analysis of >300 samples in our laboratory over the last 6 months.


Assuntos
Benzodiazepinas/metabolismo , Hipnóticos e Sedativos/metabolismo , Detecção do Abuso de Substâncias/métodos , Alprazolam/análogos & derivados , Compostos Azabicíclicos/sangue , Compostos Azabicíclicos/metabolismo , Compostos Azabicíclicos/urina , Benzodiazepinas/sangue , Benzodiazepinas/urina , Cromatografia Líquida/métodos , Diazepam/análogos & derivados , Toxicologia Forense , Humanos , Hipnóticos e Sedativos/análise , Hipnóticos e Sedativos/sangue , Hipnóticos e Sedativos/urina , Limite de Detecção , Piperazinas/sangue , Piperazinas/metabolismo , Piperazinas/urina , Medicamentos Indutores do Sono/sangue , Medicamentos Indutores do Sono/metabolismo , Medicamentos Indutores do Sono/urina , Extração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Zolpidem/sangue , Zolpidem/metabolismo , Zolpidem/urina
5.
Leg Med (Tokyo) ; 47: 101765, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32769017

RESUMO

Quantitative analysis of thiosulfate is useful for diagnosing hydrogen sulfide poisoning. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) enables more rapid and sensitive measurements than previous methodologies. As simple measurements of blood thiosulfate concentration are affected by the blood matrix, blood is used as the solvent to prepare the standard solution for calibration curve generation. Thus, a large amount of blood devoid of thiosulfate is required. We developed a preparation method by incorporating an ultrafiltration step to overcome this limitation and generate a calibration curve using a standard solution prepared with pure water. We used this improved method to investigate the stability of thiosulfate in refrigerated samples. To compare the effects of refrigeration, blood samples were prepared using the following two methods: one sample was treated with a 50-kDa exclusion ultrafiltration membrane and the other was not treated. The samples were stored at 4 °C, and then measured at 0, 3, 6, 24, 48, and 96 h. The incorporation of the ultrafiltration step in the measurement procedure enabled the quantification of thiosulfate, by plotting a calibration curve using a standard of pure water; it did not require a blood standard. Additionally, the reduction in whole blood thiosulfate concentration was within 10% during 2 days of refrigeration. Thus, the need for a large amount of blood to prepare the standard solution was resolved by the ultrafiltration step in test sample preparation. This method is useful to measure thiosulfate concentration and is not hindered by sample refrigeration for a few days.


Assuntos
Toxicologia Forense/métodos , Sulfeto de Hidrogênio/envenenamento , Manejo de Espécimes/métodos , Tiossulfatos/sangue , Ultrafiltração/métodos , Calibragem , Humanos , Refrigeração , Soluções , Água
6.
Fa Yi Xue Za Zhi ; 36(3): 347-353, 2020 Jun.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32705848

RESUMO

Abstract: Metabolomics is an interdisciplinary subject that rose in the post-genomic era, which focuses on quantitative study of the response of living organisms to outside stimulation and pathophysiological changes, as well as multiple dynamic response of the level of in vivo metabolites caused by genetic mutation. It is extensively used in basic research of system biology, materia medica, clinical medicine, etc. In the forensic field, metabolomics mainly focuses on forensic toxicology, but with the generalization of certain techniques, it's foreseeable that metabolomics has a broad research prospect in forensic pathology. This article summarizes the major analysis techniques and methods of metabolomics, describes the research status of metabolomic techniques in the field of forensic pathology application research, including postmortem interval and death cause. Moreover, this article summarizes and discusses the potential applicable areas, in order to provide reference for relative research and application.


Assuntos
Patologia Legal , Metabolômica , Mudanças Depois da Morte , Autopsia , Patologia Legal/tendências , Toxicologia Forense , Humanos
7.
J Anal Toxicol ; 44(7): 718-733, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32672807

RESUMO

A method for analyzing Δ9-tetrahydrocannabinol (THC), 11-hydroxy-Δ9-THC (THC-OH) and 11-nor-Δ9-THC-9-carboxylic acid (THC-COOH) in postmortem solid specimens using liquid chromatography-tandem mass spectrometry was developed and validated. A Stomacher instrument was used to prepare these tissues before extraction. Prior to solid phase extraction, liver, kidney, stomach, lung, brain, muscle, bladder and intestine tissues were pretreated with alkaline hydrolysis. All calibration curves were found to be linear with coefficients of determination greater than 0.99. The limit of quantification was 1.0 ng/g. Using three controls, within-run precision ranged between 1.0 and 12.0%, between-run precision ranged between 1.0 and 6.0%, and accuracy ranged between -7.0 and 8.0%. Matrix effects ranged from -21 to 24%. After matrix effects were excluded, analytical recoveries ranged from 79 to 97%. The distributions of THC, THC-OH and THC-COOH were investigated in 32 postmortem cases that tested positive for cannabinoids. This revealed new information regarding the distribution of THC metabolites in stomach, intestine and bladder. Alkaline hydrolysis was sufficient for the deglucuronidation of THC-COOH-glucuronide to its free form, THC-COOH, in all tissues of interest. In conclusion, measuring THC and its metabolites (THC-OH and THC-COOH) in tissues is crucial for any forensic toxicology detection method, especially when bodies are heavily decomposed, as solid tissues may be the only specimens available for testing.


Assuntos
Dronabinol/análise , Toxicologia Forense , Detecção do Abuso de Substâncias/métodos , Cromatografia Líquida , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem
8.
J Anal Toxicol ; 44(7): 741-746, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32591773

RESUMO

Neonatal drug exposure is currently assessed using meconium, urine, blood, hair, or umbilical cord tissue/blood. Due to the invasiveness, challenges, and limitations of collection, and/or analytical difficulties of these matrices, oral fluid may be a more desirable matrix in diagnosing opioid exposure and risk for opioid withdrawal in neonatal abstinence syndrome. Traditional oral fluid collection devices are not viable options as they are too large for neonates' mouths and may contain chemicals on the collection pad. Unstimulated and stimulated infant oral fluid samples have been used for therapeutic drug monitoring as an alternative matrix to blood. The objective of this study was to assess the viability of a simple oral fluid collection system using a sterile foam-tipped swab rinsed in phosphate-buffered saline. Two infants were administered fentanyl for post-operative pain relief while hospitalized in the Neonatal Intensive Care Units at the Children's Hospital of Richmond of Virginia Commonwealth University. Oral fluid samples were collected at 16 h, 2 days, and/or 7 days following the start of intravenous infusion of fentanyl. Samples were analyzed by ultra-high-pressure liquid chromatography-tandem mass spectrometry for fentanyl and norfentanyl after solid-phase extraction. In one of the three samples tested, fentanyl and norfentanyl were detected at concentrations of 28 and 78 ng/mL, respectively. Based on the infusion rate, the theoretical oral fluid fentanyl concentration at steady state was calculated to be 33 ng/mL.


Assuntos
Fentanila/metabolismo , Saliva/metabolismo , Toxicologia Forense , Humanos , Lactente , Recém-Nascido , Extração em Fase Sólida
9.
J Anal Toxicol ; 44(7): 679-687, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32591789

RESUMO

Synthetic cathinones, commonly referred to as "bath salts," are powerful amphetamine-like psychostimulants, and new derivatives are constantly appearing in the illicit market to evade judicial consequences. To keep up with these new stimulant drugs, a low-sample-size liquid chromatography-tandem mass spectrometry method was validated to quantify 30 synthetic cathinones in postmortem blood including N-ethylpentylone and eutylone. Mixed mode cation exchange solid-phase extraction using 0.25 mL postmortem blood was performed followed by detection using a triple quadrupole mass spectrometer operating electrospray ionization in positive mode. The reversed-phase chromatographic separation was achieved in 16 min, resolving all isobaric compounds. The linear range of the calibration curve was 1-500 ng/mL (R  2 > 0.99) for all compounds. Limit of quantification (LOQ) and limit of detection were determined to be at 1 ng/mL. Both imprecision and bias were evaluated and had met all allowed criteria (CV and bias <20%). No matrix effect was observed with values ranging from -5.1 to 13.3% (CV 11.4-17.5%, n = 10). Extraction efficiency (84.9-91.5%) and process efficiency (86.1-102.6%) were satisfactory, except for 4-chloroethcathinone which was 63 and 64.9%, respectively. No carryover after the upper LOQ was detected. Neither endogenous nor exogenous interferences were observed. Both dilution integrity and stability (24 h) yielded acceptable results. This method was applied to 18 postmortem cases received between 2015 and 2019. Eight different synthetic cathinones were detected in selected postmortem cases within the past 5 years, showing a wide range of concentrations from 1.4 to >500 ng/mL. While ethylone and methylone were detected in 2015, cases between 2016 and 2017 were predominantly butylone, dibutylone, pentylone and N-ethylpentylone which had also exhibited a significant increase in 2018. To our knowledge, this method is the most comprehensive methodology for the determination of up-to-date synthetic cathinones currently available in whole blood.


Assuntos
Alcaloides/análise , Toxicologia Forense , Detecção do Abuso de Substâncias , Cromatografia Líquida , Humanos , Limite de Detecção , Espectrometria de Massas em Tandem
10.
Fa Yi Xue Za Zhi ; 36(2): 216-222, 2020 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32530170

RESUMO

Abstract: Objective To investigate the maximum allowable deviations of retention time and ion abundance ratio of the 8 common drugs (poisons) from 3 categories, poisons (methamphetamine, morphine, ketamine), benzodiazepines (estazolam, midazolam, diazepam, clonazepam) and barbiturates (phenobarbital) in blood, by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in forensic toxicology analysis. Methods The deviations of retention time and ion abundance ratio at 7 low mass concentrations, limit of detection (LOD), 2LOD, limit of quantitation (LOQ), 1.5LOQ, 2LOQ, 4LOQ and 6LOQ, were tested by LC-MS/MS after liquid-liquid extraction under the conditions of two chromatographic columns and three chromatographs. Results The deviation of absolute retention time of 98.11% of 8 drugs (poisons) in the blood samples was within the range of ±0.05 min, and that of the relative retention time of 96.21% was within the range of ±0.4%. The maximum deviation of the ion abundance ratio was highly correlated with the mass concentration. When the mass concentration of drugs (poisons) was LOQ or above, more than 95% of the absolute deviation and relative deviation of the ion abundance ratio were in the range of ±25% and ±40%, respectively; when the mass concentration was below LOQ, the range could be expanded to ±35% and ±50%, respectively. Conclusion It is recommended for the determination range of the absolute retention time deviation of 8 common drugs (poisons) to be ±0.1 min and that of the relative retention time deviation to be ±1.0%. The determination range of absolute deviation of the ion abundance ratio should be ±25% when the mass concentration is LOQ or above, and the relative deviation should be ±40%. When the mass concentration is below LOQ, the deviation determination range can be expanded to ±35% and ±50%, respectively.


Assuntos
Espectrometria de Massas em Tandem , Cromatografia Líquida , Toxicologia Forense , Extração Líquido-Líquido , Venenos
11.
Leg Med (Tokyo) ; 46: 101717, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32442861

RESUMO

In this study quetiapine and pregabalin were analyzed in human bones. A method previously developed for the determination of antidepressants in human bone was tested for the analysis of these two substances. Bones were pulverized and subjected to the extraction protocol, and after undergoing solid-phase extraction, samples were analyzed using gas chromatography-mass spectrometry. The assay was validated in the range 0.3-500 ng/mg, mean analytical recovery was 76.9% for quetiapine and 90.9% for pregabalin, matrix effect was 83% for quetiapine and 91% for pregabalin and process efficiency was 63.8% for quetiapine and 82.7% for pregabalin. The intra- and inter-day precision was below 3% in all cases and the intra- and inter-assay accuracy values were in almost all cases better than 12%. The validated method was then applied to bone samples from forensic cases. Drugs were detected in bone in 2 of the 3 blood positive cases. The approximate concentrations in bone were 40 ng/mg for pregabalin and 7 ng/mg for quetiapine. To our knowledge, this is the first time these substances were detected in bones. With this study the number of substances with a validated protocol to be used in human bones in case of necessity is expanded.


Assuntos
Antidepressivos/análise , Osso e Ossos/metabolismo , Toxicologia Forense/métodos , Pregabalina/análise , Fumarato de Quetiapina/análise , Antidepressivos/isolamento & purificação , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Pregabalina/isolamento & purificação , Fumarato de Quetiapina/isolamento & purificação
12.
J Anal Toxicol ; 44(7): 747-751, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-32382735

RESUMO

A 23-month-old boy was brought to a medical center by his mother, as she noticed that the father has gripped him around the neck and this had left marks. As a result of this, a child protection medical examination was requested. However, there was a significant chronology of mental health issues in the mother. Among the mother's medications, quetiapine and propranolol were the more active. Given a consultant pediatrician was concerned that the boy was vulnerable and potentially has experienced neglect and physical harm, the local authority instructed a hair test to document possible poisoning. However, this occurred several months later, due to court delays (postponed hearings and decisions) when the child was 32-month old. The laboratory received a strand of hair of the child (12 cm in length, light brown in color) and a strand of hair of the mother (>20 cm in length, dark in color) with the request to test both specimens by segmentation (12 x 1 cm) for quetiapine, an anti-psychotic drug and propranolol, a ß-blocker agent. After decontamination and segmentation, the specimens were incubated in borate buffer pH 9.5 and extracted by a mixture of ether/dichloromethane/hexane/isoamyl alcohol to test for the drugs, including norquetiapine by a specific LC-MS-MS method. The first 3 cm segments of the child's hair were free of drug, roughly corresponding to the period he was no more in contact with the mother. Propranolol tested positive in the other segments at 15-72 pg/mg, with a linear increase from the proximal to the distal end. This was also observed for quetiapine, with concentrations in the range 10-18 pg/mg. Norquetiapine was never identified in the child's hair. The following concentrations were observed in the mother's hair: 6028-10,284, 910-4576 and 1116-6956 pg/mg for propranolol, quetiapine and norquetiapine, respectively. This confirmed that the donor was a long-term repetitive user of propranolol and quetiapine. The hair test results have indicated that the child was in contact with propranolol and quetiapine for a long period. It is not possible to put a temporal period for each segment, as the hair growth at the age of 32 months is not the same as for an adult (difference in the duration of the anagen period), nor to put any quantitative dosage or frequency of exposure(s) when interpreting the data. An increase of concentrations from root to tip was observed which is considered highly indicative of external contamination, with the older hair segments (those which are the more concentrated) being in contact for a longer time with contaminated items (hands of the mother, home items such as furniture, dishes, beddings, etc.). Overinterpreting drug findings in hair can have very serious legal implications in child protection cases, particularly when no other toxicological test and no clinical report exist to support voluntary administration of drugs. Whatever the findings, a proper interpretation of hair test results is critical and should be done ideally with other information available, such as medical history, witness statements and the available circumstances of the matter. A single hair test should not be used to determine long-term exposure to a drug.


Assuntos
Toxicologia Forense/métodos , Cabelo/química , Propranolol/análise , Fumarato de Quetiapina/análise , Maus-Tratos Infantis , Pré-Escolar , Humanos , Masculino
13.
Fa Yi Xue Za Zhi ; 36(1): 45-51, 2020 Feb.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32250078

RESUMO

Abstract: Objective To establish an analysis method for simultaneous determination of 13 sedative substances and their metabolites in blood by liquid-liquid extraction and liquid chromatography-tandem mass spectrometry (LC-MS/MS) technology and to apply the method to actual cases. Methods The samples were extracted with ethyl acetate after an internal standard was added. The extract was condensed until it was nearly dry and then its residues were dissolved with methanol, filtered through 0.22 µm filter and finally determined. The 13 sedative substances and their metabolites were separated through the C18 chromatographic column, then gradient elution was performed on them with methanol and 20 mmol/L ammonium formate (containing 0.1% formic acid) solution. After that, they were determined in the electrospray positive ion mode and quantified by internal standard method. Results The 13 sedative substances and their metabolites in blood showed good linearity in the range of 5-200 µg/L with correlation coefficients ranging from 0.990 3 to 0.999 8. The detection limits were 0.1-1.0 µg/L. Recovery rates of sedative substances were in the range of 71.2%-93.4% when solutions with concentrations of 10, 50 and 200 µg/L were added. The deviations of intra-day and inter-day relative standard deviations (RSD) were not more than 8.6%. Accuracies (bias) were within ±9.8%. Conclusion This method is rapid, simple, effective and sensitive, and can be applied to analysis of 13 sedative substances and their metabolites in blood in forensic toxicology.


Assuntos
Hipnóticos e Sedativos , Espectrometria de Massas em Tandem , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Toxicologia Forense
14.
Fa Yi Xue Za Zhi ; 36(2): 157-163, 2020 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: covidwho-15796

RESUMO

Abstract: Chloroquines are the long-established prescription drug, which are often used clinically to treat malaria and connective tissue diseases. Since December 2019, corona virus disease 2019 (COVID-19) outbreaks caused by 2019 novel coronavirus (2019-nCoV) has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against 2019-nCoV need to be quickly screened. The antimalarial drug chloroquine phosphate which has already been approved is confirmed to have an anti-2019-nCoV effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The current dosage recommended in clinical treatment is larger than that in previous treatment of malaria and the period of treatment is longer. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.


Assuntos
Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , China , Toxicologia Forense , Humanos , Pandemias
15.
Fa Yi Xue Za Zhi ; 36(2): 157-163, 2020 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: covidwho-599585

RESUMO

Abstract: Chloroquines are the long-established prescription drug, which are often used clinically to treat malaria and connective tissue diseases. Since December 2019, corona virus disease 2019 (COVID-19) outbreaks caused by 2019 novel coronavirus (2019-nCoV) has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against 2019-nCoV need to be quickly screened. The antimalarial drug chloroquine phosphate which has already been approved is confirmed to have an anti-2019-nCoV effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The current dosage recommended in clinical treatment is larger than that in previous treatment of malaria and the period of treatment is longer. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.


Assuntos
Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , China , Toxicologia Forense , Humanos , Pandemias
16.
Fa Yi Xue Za Zhi ; 36(2): 157-163, 2020 Apr.
Artigo em Inglês, Chinês | MEDLINE | ID: mdl-32212512

RESUMO

Abstract: Chloroquines are the long-established prescription drug, which are often used clinically to treat malaria and connective tissue diseases. Since December 2019, corona virus disease 2019 (COVID-19) outbreaks caused by 2019 novel coronavirus (2019-nCoV) has occurred in China and many countries around the world. Due to the lack of drugs against COVID-19, the disease spreads rapidly and the mortality rate is relatively high. Therefore, specific drugs against 2019-nCoV need to be quickly screened. The antimalarial drug chloroquine phosphate which has already been approved is confirmed to have an anti-2019-nCoV effect and has been included in diagnostic and therapeutic guidelines. However, awareness of the risk of chloroquine phosphate causing acute poisoning or even death should be strengthened. The current dosage recommended in clinical treatment is larger than that in previous treatment of malaria and the period of treatment is longer. Many provinces have required close clinical monitoring of adverse reactions. This paper reviews the pharmacological effects, poisoning and toxicological mechanisms, in vivo metabolism and distribution, and forensic issues of chloroquine drugs, in order to provide help to forensic practice and clinical work.


Assuntos
Cloroquina/efeitos adversos , Cloroquina/uso terapêutico , Infecções por Coronavirus/tratamento farmacológico , Pneumonia Viral/tratamento farmacológico , Betacoronavirus , China , Toxicologia Forense , Humanos , Pandemias
17.
Forensic Sci Int ; 308: 110175, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32032869

RESUMO

Recently, there has been an increase in overdose deaths due to novel synthetic opioids (NSO). Due to backlogs experienced by many forensic laboratories, it is important to understand drug stability in a variety of storage conditions. The objective of this study was to investigate the stability of AH-7921, U-47700, U-49900, U-50488, MT-45, W-15, and W-18 in blood at various temperatures over a 36-week period. NSO were generally stable over the 36-week period (66%-118%) at low and high concentrations when blood samples were stored in the refrigerator or freezer. Most analytes were stable for at least 2 weeks at room temperature (77%-120%). At the elevated temperature (35°C), analytes were generally stable for at least 14 days (75%-109%). This study has determined the stability of several NSO at various temperatures over a 36-week period. These results reflect the forensic significance of keeping samples stored at proper temperatures. Blood samples suspected to contain synthetic opioids should be stored refrigerated or frozen, when possible, in order to preserve analyte stability, especially at low concentrations.


Assuntos
Analgésicos Opioides/sangue , Analgésicos Opioides/química , Estabilidade de Medicamentos , Manejo de Espécimes , Medicamentos Sintéticos , Temperatura , (trans)-Isômero de 3,4-dicloro-N-metil-N-(2-(1-pirrolidinil)-ciclo-hexil)-benzenoacetamida/sangue , Animais , Benzamidas/sangue , Bovinos , Toxicologia Forense , Piperazinas/sangue
18.
Sci Rep ; 10(1): 1974, 2020 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-32029797

RESUMO

The finding that drugs and metabolites can be detected from fingerprints is of potential relevance to forensic science and as well as toxicology and clinical testing. However, discriminating between dermal contact and ingestion of drugs has never been verified experimentally. The inability to interpret the result of finding a drug or metabolite in a fingerprint has prevented widespread adoption of fingerprints in drug testing and limits the probative value of detecting drugs in fingermarks. A commonly held belief is that the detection of metabolites of drugs of abuse in fingerprints can be used to confirm a drug has been ingested. However, we show here that cocaine and its primary metabolite, benzoylecgonine, can be detected in fingerprints of non-drug users after contact with cocaine. Additionally, cocaine was found to persist above environmental levels for up to 48 hours after contact. Therefore the detection of cocaine and benzoylecgonine (BZE) in fingermarks can be forensically significant, but do not demonstrate that a person has ingested the substance. In contrast, the data here shows that a drug test from a fingerprint (where hands can be washed prior to donating a sample) CAN distinguish between contact and ingestion of cocaine. If hands were washed prior to giving a fingerprint, BZE was detected only after the administration of cocaine. Therefore BZE can be used to distinguish cocaine contact from cocaine ingestion, provided donors wash their hands prior to sampling. A test based on the detection of BZE in at least one of two donated fingerprint samples has accuracy 95%, sensitivity 90% and specificity of 100% (n = 86).


Assuntos
Cocaína/análogos & derivados , Cocaína/metabolismo , Toxicologia Forense/métodos , Pele/química , Detecção do Abuso de Substâncias/métodos , Cocaína/isolamento & purificação , Transtornos Relacionados ao Uso de Cocaína/diagnóstico , Dermatoglifia , Desinfecção das Mãos , Humanos , Irlanda , Espectrometria de Massas , Sensibilidade e Especificidade , Pele/metabolismo , Fatores de Tempo
19.
J Anal Toxicol ; 44(6): 570-579, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32020200

RESUMO

Sampling and drug stability in oral fluid (OF) are crucial factors when interpreting forensic toxicological analysis, mainly because samples may not be analyzed immediately after collection, potentially altering drug concentrations. Therefore, the stability of some common drugs of abuse (morphine, codeine, 6-monoacetylmorphine, cocaine, benzoylecgonine, Δ9-tetrahydrocannabinol, cannabidiol, amphetamine, 3,4-methylenedioxymethamphetamine, ketamine) and the more commonly consumed new psychoactive substances in our environment (mephedrone, and N-(adamantan-1-yl)-1-(5-fluoropentyl)-1H-indazole-3-carboxamide 5F-AKB48 also known as 5F-APINACA) was investigated in an OF pool for the presence and absence of M3 Reagent Buffer® up to 1 year of storage. Fortified OF samples were stored at three different temperatures (room temperature, 4 and -20°C) to determine the best storage conditions over time. Control fortified OF samples were stored at -80°C for reference purposes. Compounds with concentration changes within ±15% of initial value were considered stable. The drugs were significantly more stable in M3 Reagent Buffer® than in neat OF samples in all storage conditions. All analytes were stable for 1 year at 4°C and -20°C in M3 Reagent Buffer®. Drugs stability in OF varied depending on the analyte, the presence of a stabilizer, the storage duration and temperature. When immediate sample analysis is not possible, we suggest to store OF samples at 4 or -20°C and test them within 2 weeks. Alternatively, OF samples may be stored at 4 or -20°C with M3 Reagent Buffer® to be tested within 1 year.


Assuntos
Estabilidade de Medicamentos , Toxicologia Forense , Psicotrópicos/química , Detecção do Abuso de Substâncias , Anfetamina , Cocaína/análogos & derivados , Codeína , Drogas Ilícitas , Metanfetamina/análogos & derivados , Morfina , Derivados da Morfina , N-Metil-3,4-Metilenodioxianfetamina , Manejo de Espécimes
20.
J Anal Toxicol ; 44(6): 580-588, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32064503

RESUMO

An LC-MS-MS method for the determination of 14 benzodiazepines (BZDs) (alprazolam, α-hydroxyalprazolam, clonazepam, bromazepam, diazepam, nordiazepam, lorazepam, lormetazepam, oxazepam, flunitrazepam, 7-aminoflunitrazepam, triazolam, midazolam and zolpidem) and 15 antidepressants (ADs) (amitriptyline, nortriptyline, imipramine, desipramine, clomipramine, norclomipramine, fluoxetine, norfluoxetine, sertraline, norsertraline, paroxetine, venlafaxine, desmethylvenlafaxine, citalopram and desmethylcitalopram) in meconium was developed and validated. Meconium samples (0.25 ± 0.02 g) were homogenized in methanol and subjected to mixed-mode cation exchange solid-phase extraction. Chromatographic separation was performed in reversed phase, with a gradient of 0.1% formic acid in 2 mM ammonium formate and acetonitrile. Two different chromatographic gradient methods were employed, one for the separation of ADs and another for BZDs. Analytes were monitored by tandem mass spectrometry employing electrospray positive mode in MRM mode (2 transitions per compound). Method validation included: linearity [n = 5, limit of quantification (LOQ) to 400 ng/g], limits of detection (n = 6, 1-20 ng/g), LOQ (n = 9, 5-20 ng/g), selectivity (no endogenous or exogenous interferences), accuracy (n = 15, 90.6-111.5%), imprecision (n = 15, 0-14.6%), matrix effect (n = 10, -73 to 194.9%), extraction efficiency (n = 6, 35.9-91.2%), process efficiency (n = 6, 20.1-188.2%), stability 72 h in the autosampler (n = 3, -8.5 to 9%) and freeze/thaw stability (n = 3, -1.2 to -47%). The method was applied to four meconium specimens, which were analyzed with and without hydrolysis (enzymatic and alkaline). The authentic meconium samples tested positive for alprazolam, α-hydroxyalprazolam, clonazepam, diazepam, nordiazepam, fluoxetine, norfluoxetine, clomipramine and norclomipramine. Therefore, the present LC-MS-MS method allows a high throughput determination of the most common BZDs and ADs in meconium, which could be useful in clinical and forensic settings.


Assuntos
Antidepressivos/análise , Benzodiazepinas/análise , Toxicologia Forense , Mecônio/química , Detecção do Abuso de Substâncias/métodos , Alprazolam/análogos & derivados , Cromatografia Líquida , Clonazepam , Humanos , Limite de Detecção , Nordazepam , Oxazepam , Reprodutibilidade dos Testes , Extração em Fase Sólida , Espectrometria de Massas em Tandem , Cloridrato de Venlafaxina , Zolpidem
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