Dextromethorphan is a widely used clinical antitussive, while its enantiomer, levomethorphan, is a controlled substance. Chiral separation and trace detection of the two enantiomers in biological samples are critically important. Herein, a micro-solid-phase extraction method coupled with enantioselective ultra-high performance liquid chromatography-mass spectrometry (UHPLC-MS) was proposed for the analysis of methorphan enantiomers. MOF-199/cellulose aerogel spheres fabricated via a facile in situ growth strategy were employed as the sorbent. By immersing Cu[2+]-rich cellulose aerogel in H3BTC (1,3,5-benzene tricarboxylate) solutions at varied concentrations, MOF-199/cellulose aerogels with tunable MOF-199 loadings (28.8%, 38.1%, 43.8%) were fabricated. Characterization results verified that MOF-199 was uniformly anchored in the pore channels of cellulose aerogel, which not only enhanced its specific surface area from 33.9 to 143.6 m[2]/g, but also mitigated the aggregation and poor recyclability of powdered MOF-199. The electrostatic attraction, chelation, and hydrogen-bonding interactions accounted for the effective extraction for dextro- and levo-methorphan. Under optimized conditions, this method exhibited favorable linearity in the range of 0.02-10.0 µg/L, with intra- and inter-day precisions of 4.9%-5.0% and 7.7%-9.7%, respectively. The limits of detection were 0.01-0.02 µg/L, respectively. Recoveries of dextro- and levo-methorphan from urine and hair samples were in the ranges of 88.9%-119.3% and 78.6%-115.7%, respectively. This method provides an effective strategy for the determination of methorphan enantiomers in biological samples, featuring rapid pretreatment, low organic solvent consumption, as well as facile operation.

Imlunestrant is a next-generation, oral, selective estrogen receptor degrader approved for treating adults with estrogen receptor-positive, human epidermal growth factor receptor 2-negative, ESR1-mutated advanced/metastatic breast cancer. Imlunestrant is metabolized partly by cytochrome P450 (CYP)3A4 oxidation and conjugation with glucuronic acid and sulfate; thus, pharmacokinetic and drug-drug interaction (DDI) studies for treatments utilizing similar pathways are essential for clinical development. Three open-label, phase 1 studies enrolled 182 healthy females of nonchildbearing potential to assess the tolerability, safety, and pharmacokinetics of imlunestrant as monotherapy or coadministered with other drugs. Drug concentrations were quantified by validated liquid chromatography-mass spectrometry. Participants tolerated imlunestrant at 200-800-mg doses, alone or with a CYP3A inhibitor (itraconazole), CYP3A inducer (carbamazepine), P-glycoprotein (P-gp) inhibitor (quinidine), and substrates of CYP2C8 (repaglinide), CYP2C19 (omeprazole), CYP2D6 (dextromethorphan), CYP3A (midazolam), P-gp (digoxin), and BCRP (rosuvastatin). Frequent treatment-related adverse events included headache (range, 4%-20%), diarrhea (2%-20%), and constipation (0%-16%). In the presence of imlunestrant, exposures (AUC0-∞) increased for dextromethorphan 1.33-fold (90% CI, 1.22-1.46), digoxin 1.39-fold (1.22-1.59), and rosuvastatin 1.49-fold (1.14-1.97). Imlunestrant exposure (AUC0-∞) decreased in combination with quinidine (CYP2D6 inhibitor) 0.87-fold (90% CI, 0.76-1.00) and carbamazepine (CYP3A4 inducer) 0.58-fold (0.49-0.69), but increased in combination with itraconazole (CYP3A4 inhibitor) 2.11-fold (1.77-2.53). Imlunestrant had no DDIs with CYP2C8 (repaglinide), CYP2C19 (omeprazole), and CYP3A4 (midazolam) substrates, or a P-gp inhibitor (quinidine), but weakly inhibited dextromethorphan (CYP2D6 substrate), digoxin (P-gp substrate), and rosuvastatin (BCRP substrate) clearance. Thus, considerations should be taken when imlunestrant is coadministered with strong CYP3A4 inhibitors, strong CYP3A4 inducers, and CYP2D6 and P-gp substrates where small changes in exposure may lead to toxicities.

Traumatic brain injury (TBI) is a major cause of morbidity and mortality worldwide. Agitation is a common complication after moderate to severe TBI and managing it in the acute hospital setting can be challenging.

Recently, abuse and fatal overdoses of over-the-counter (OTC) medications have become serious social and health issues worldwide. However, many drug components in OTC medications that are abused have different chemical structures from those assessed by commercially available rapid drug test kits. In this research, we focused on using dried blood spot (DBS) samples to develop a simple and accurate method for forensic toxicological analysis of drugs of interest in deaths by poisoning. We combined the DBS method with liquid chromatography coupled with electrospray ionization-tandem mass spectrometry to quantify eight OTC drug components (apronal, caffeine, chlorpheniramine, dextromethorphan, diphenhydramine, diprophylline, noscapine, and promethazine). The linearities of the calibration curves were good in the concentration range of 0.1-2.0 μg/mL. The method achieved repeatable and accurate quantification of the eight target drugs with intra- and inter-assay coefficients of variation of below 13.0% and 12.6%, respectively. Comparison with our general practice method showed good positive correlations at the quantifiable concentrations of all drugs. Furthermore, when applied to an actual case, it was possible to diagnose death by drug poisoning, confirming the usefulness of this method.

BACKGROUND Drug abuse is a global public health concern with substantial medical, psychological, and social consequences. Drug abuse monitoring (DAM) systems help identify patterns of substance misuse and support regulatory interventions. Current monitoring systems mainly rely on fixed-point reporting from addiction treatment centers, detention facilities, and compulsory detoxification institutions, which can lead to delayed detection and incomplete data coverage. Additionally, there is increasing misuse of prescription medications, over-the-counter drugs, and emerging psychoactive substances in medical settings. Therefore, establishment of a structured DAM approach within medical institutions is important to improve early detection and reporting of drug abuse. MATERIAL AND METHODS A single-center retrospective observational study was conducted at Wuxi Mental Health Centre to monitor patients diagnosed with drug/substance abuse between September 2020 and December 2024. A DAM research group was established to standardize reporting procedures, define staff responsibilities, and implement monitoring protocols linked to the national reporting system. RESULTS In total, 146 patients with drug/substance abuse were monitored: 41 male individuals (28.08%) and 105 female individuals (71.92%). Nineteen drugs or substances across 5 categories were identified. Sedative-hypnotic drugs represented the largest proportion of cases (98.63%). Antipyretic and analgesic drugs containing caffeine were abused in 4.11% of cases; dextromethorphan or Yumei tablets were involved in 3.42% of cases. Nitrous oxide abuse was identified in 2.05% of all monitored cases; affected patients were aged 17 to 25 years. CONCLUSIONS The proposed DAM approach was successfully implemented in a hospital setting and demonstrated feasibility for systematic monitoring of drug abuse in medical institutions.

While antidepressants may be the drug of choice for depression, they also have FDA approval as treatments for other medical disorders. For example, antidepressants are useful in the treatment of obsessive-compulsive disorder, social phobia, panic disorder, generalized anxiety disorder (GAD), and post-traumatic stress disorder (PTSD). Antidepressants also have non-FDA approved, off-label indications. This activity reviews the indications, contraindications, activity, adverse events, and other key elements of antidepressant therapy in the clinical setting as relates to the essential points needed by members of an interprofessional team managing the care of patients receiving antidepressant medications for conditions that respond to this medication class.

A 16-year-old post-pubertal female presented with mixed anxiety-depressive symptoms, prominent obsessive rumination, relationship-centered guilt, reassurance-seeking, fantasy intrusions, and difficulty separating fantasy from reality during periods of distress. Baseline scores were in the moderate range for depression and severe range for anxiety, with a Patient Health Questionnaire-9 score of 14 and a Generalized Anxiety Disorder-7 score of 20. A low-to-moderate-intensity Cheung glutamatergic regimen-like strategy was introduced, consisting of dextromethorphan, a CYP2D6-inhibiting antidepressant, and piracetam, with risperidone co-prescribed for fantasy-related cognitions, overvalued ideas, and obsessive instability. Across the follow-up period from January to June 2026, depressive symptoms improved to the minimal-to-mild range, and anxiety symptoms improved to the mild range, with Patient Health Questionnaire-9 scores mostly between 4 and 6 and Generalized Anxiety Disorder-7 scores mostly between 6 and 7, except for one stress-related rise to 11. Obsessional symptoms reportedly reduced by more than 30% after dextromethorphan escalation and piracetam introduction. Later improvements included better ability to interrupt rumination, reduced preoccupation with "pretending to be ill," shorter fantasy intrusions, and improved fantasy-reality differentiation. No medication side effects, dissociation, hypomania, serotonin-toxicity symptoms, sleep disruption, appetite loss, or renewed self-harm ideation were documented. The clinically distinctive feature was a discordant response pattern as follows: repetitive, obsessive, and fantasy-related intrusions appeared to loosen more clearly than attachment-linked emotional reactivity. The course is compatible with the hypothesis that N-methyl-D-aspartate and α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (NMDA-AMPA) modulation may help selected post-pubertal adolescents disengage from rigid perseverative loops. However, interpretation is limited by polypharmacy, risperidone titration, selective serotonin reuptake inhibitor (SSRI) effects, supportive care, natural symptom fluctuation, and the absence of formal obsessive-compulsive ratings or withdrawal/rechallenge. This case is best viewed as hypothesis-generating.

A rapid, sensitive, and selective LC-MSMS method was developed and validated for the quantification of dextromethorphan (DXM), pseudoephedrine (PSE), olanzapine (OLA), and fluoxetine (FLU) in human plasma. Mixture 1 (DXM/PSE) and mixture 2 (OLA/FLU) are fixed-dose combinations commonly misused at high doses for their euphoric effects. The proposed method employed a simple protein precipitation technique for sample preparation, using a cost-effective cross-over internal standard strategy; OLA for mixture 1 and DXM for mixture 2. Chromatographic separation was achieved on a Hypersil GOLD column (100 × 3 mm, 1.9 µm) using an isocratic mobile phase consisting of acetonitrile and 0.1% formic acid (70:30, v/v) at a flow rate of 0.3 mL/min. The short runtime of 2.5 min enables high-throughput analysis. Detection was performed in positive ionization mode using multiple reaction monitoring (MRM). The method exhibited linearity over concentration ranges of 0.05-25.0 ng/mL for DXM, 2.0-1000.0 ng/mL for PSE, 0.2-20.0 ng/mL for OLA, and 0.5-50.0 ng/mL for FLU with lower limits of quantification (LLOQs) of 0.05, 2.0, 0.2, and 0.5 ng/mL, respectively. The method was successfully validated in accordance with FDA and ICH bioanalytical method validation guidelines, demonstrating satisfactory selectivity, accuracy, and precision. The validated method demonstrated high extraction recovery (> 90%), limited, reproducible matrix effects (IS-normalized matrix factor CV ≤ 15%). This study represents a novel application of artificial intelligence (AI)-assisted evaluation, utilizing a universally accessible model to assess the greenness and whiteness of the proposed LC-MS/MS method through the Auto-AGREE and Auto-RGB 12 frameworks. The AI-generated assessments demonstrated high agreement with traditional metrics, highlighting the potential of AI tools to provide rapid and objective holistic sustainability evaluations for the global analytical community.

This study investigated the effects of Shuganning Injection(SGN) on the enzymatic activities of cytochrome P450(CYP450) and its interaction with bicyclol(BIC). In vitro assessments were performed utilizing the Cocktail probe drug method in combination with a human liver microsome incubation system. UPLC-MS/MS analysis revealed that SGN inhibited the enzymatic activities of CYP1A2, CYP2D6, CYP2C9, CYP2C19, CYP3A4, and CYP2E1 in a concentration-dependent manner. In vivo experiments demonstrated that SGN significantly altered the pharmacokinetic parameters of caffeine, dextromethorphan, midazolam, and omeprazole in rats, primarily characterized by a marked increase in the area under the curve(AUC)(P<0.05) and a significant decrease in clearance(CL)(P<0.05). These findings suggest that SGN may inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2. After co-administration with BIC, the exposure level(AUC_(0-t)) of BIC was significantly increased, while its CL significantly decreased. Further analysis using real-time quantitative PCR and Western blot confirmed that SGN significantly downregulated the mRNA and protein expression of CYP2C19 and CYP3A2 in rat liver. The results indicate that SGN can inhibit the activities of CYP1A2, CYP2C19, CYP2D4, and CYP3A2 in rats. By inhibiting CYP2C19 and CYP3A2, SGN slowed down the metabolic clearance of BIC, leading to elevated plasma drug concentrations. These findings suggest a potential risk of increased drug exposure when SGN is used in combination with BIC in clinical practice.