液相色谱-质谱联用法测定复方氨酚烷胺胶囊人体生物等效性

目的 研究复方氨酚烷胺胶囊的人体生物等效性。方法 采用双周期交叉实验设计,22名健康男性受试者随机交叉单剂量口服复方氨酚烷胺胶囊试验制剂和参比制剂各1粒。采用液相色谱-质谱联用法测定血浆中对乙酰氨基酚（paracetamol, PAR）、金刚烷胺（amantadine, AMA）、马来酸氯苯那敏（chlorphenamine, CHL）和咖啡因（caffenine, CAF）的浓度,采用DAS3.2.5软件计算药物代谢动力学参数,并采用双侧t检验法和90%置信区间比较主要药物代谢动力学参数（cmax,tmax,t1/2和AUC0-t）。结果 受试制剂和参比制剂中PAR、AMA、CAF和CHL的AUC0→t、AUC0→∞、cmax和tmax比较,差异均无统计学意义（P>0.05）。结论 本实验方法准确、灵敏、简便,两种制剂具有生物等效性。     

Possible Fatal Acetaminophen Intoxication with Atypical Clinical Presentation

Acetaminophen or paracetamol, a commonly used over‐the‐counter analgesic, is known to elicit severe adverse reactions when taken in overdose, chronically at therapeutic dosage or, sporadically, following single assumptions of a therapeutic dose. Damage patterns including liver damage and, rarely, acute tubular necrosis or a fixed drug exanthema. We present a case of fatal acetaminophen toxicity with postmortem blood concentration 78 μg/mL and unusual clinical features, including a visually striking and massive epidermolysis and rhabdomyolysis, disseminated intravascular coagulation and myocardial ischemia. This case is compared with the most similar previous reports in terms of organ damage, clinical presentation, and cause of death. We conclude that a number of severe patterns of adverse effects to acetaminophen are emerging that were previously greatly underestimated, thus questioning the adequacy of the clinical spectrum traditionally associated with acetaminophen intoxication and leading to the need to review this spectrum and the associated diagnostic criteria.     

Acute fatal acetaminophen overdose without liver necrosis

Two unusual cases of suicidal overdose of acetaminophen (paracetamol) without the usual extensive centrilobular necrosis of the liver are reported. Both cases were subjected to comprehensive drug screening by immunoassay, and a combination of gas chromatography with mass spectrometry, nitrogen detection, and electron capture detection. Acetaminophen was detected in both cases. No other drugs were detected in case #1, and only a small amount of olanzapine (<0.1 mg/L) was detected in case #2. No anatomical cause of death was identified in either case. If untreated, the normal outcome of a large acetaminophen overdose would be massive hepatic necrosis with delayed death and low blood and tissue acetaminophen concentrations. In contrast, particularly high postmortem acetaminophen concentrations were measured in both our cases with little hepatic tissue damage. For case #1, femoral blood acetaminophen 1280 mg/L, vitreous 878 mg/L, and liver 729 mg/kg; in case #2, cardiac blood 1220 mg/L, vitreous 779 mg/L, liver 3260 mg/kg, and gastric 11,500 mg/500 g. Acetaminophen was measured using high performance liquid chromatography with UV detection (254 nm) using 3-hydroxyacetanilide as the internal standard. The very high concentrations of acetaminophen is these cases but relatively little hepatic damage suggests an alternative, possibly cardiac, mechanism of death.     

Analysis of friction ridge evidence for trace amounts of paracetamol in various pharmaceutical industries by Raman spectroscopy

The detection of potentially harmful substances presents a multifaceted challenge. On one hand, it can directly save lives, on the other, it can significantly aid and enhance police work, thereby increasing the effectiveness of investigations. The research conducted in this study primarily aims to identify paracetamol in fingerprints, considering situations involving direct contact of a person with paracetamol either chronically or in a single dose. The identification procedure presented, utilizing Raman spectroscopy, aims to rapidly detect the xenobiotic following ingestion by an individual, which involves touching the tablet with their fingers—this can be termed as touch evidence in forensic science investigations. Additionally, the authors focus on assessing the impact of additives present in drugs containing paracetamol as the main active ingredient. The screening results obtained will enable us to analyze the composition of drugs in terms of potentially toxic substances, and their influence on the physicochemical activity of the active substance. We successfully identified the paracetamol molecule using a noninvasive forensic trace detection method. Samples in the form of common drugs containing 500 mg of paracetamol were studied. Throughout the study, comprehensive validation of the method was ensured through the utilization of a statistical model, which excluded sensitivity to the presence of other substances, whether additives or from the external environment. The proposed approach to trace the content of substances in fingerprint using Raman scattering analysis provides a useful starting point to enhance current analytical methods not only in forensic science but also in toxicology.