Phenmetrazine Hydrochloride

The issue of drug abuse is increasingly becoming a significant concern worldwide. However, the simultaneous detection of a wide spectrum of drug of abuse (DOA), especially in biofluids, is challenging due to their diverse and varied physicochemical properties and matrix effects. Herein, we have developed a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for simultaneous detection of 203 DOAs, including amphetamines, opiates, cathinones, phencyclidines, synthetic cannabinoids, cocaine, and metabolites, in 100 μL of urine. A mass analysis was performed using multiple reaction monitoring mode with an electrospray ionization source. The run time of the developed method was 16 min. Two sample preparation methods were compared for urine samples: enzymatic hydrolysis followed by either dilution or QuEChERS. Both methods demonstrated good linearity and low matrix effects; however, the dilution method showed superior accuracy and precision. Method validation was conducted to assess the efficacy of the developed method. The LC-MS/MS method with the dilution method demonstrated good linearity with the coefficients of determination (R²) above 0.99 for 200 compounds. The limit of quantification (LOQ) ranged from 0.1 to 20.0 ng/mL. The inter-day precision was below 20 % for all 203 compounds, with a bias of ±20 % for 198 compounds. This method was successfully applied to 40 real urine samples. The developed method allows the simultaneous separation and detection of a variety of DOAs with diverse physicochemical properties in a small amount of urine. Furthermore, the technique could be adapted to fit the practical requirements of forensic investigations, thereby enhancing its effectiveness and reliability.

This study aims to examine the changes in metabolic profiles in patients with patent foramen ovale (PFO) and migraine, as well as in patients with isolated migraine, before and after surgical intervention using metabolomics.

Patients were categorized into four groups: the simple migraine (SM) group, the PFO with migraine preoperative group (PRE), the PFO with migraine postoperative Day 3 group (POST_3d), and the PFO with migraine postoperative Day 30 group (POST_30d). Untargeted metabolomics using liquid chromatography–mass spectrometry (LC‐MS) were employed to identify differential metabolites across these groups. Differential metabolites were identified, their clinical diagnostic value was assessed, and a correlation analysis was conducted to examine changes in metabolic pathways before and after surgery.

The expression levels of metabolites such as linoleic acid, quinolinic acid, homophenylalanine, and amphetamine showed significant changes in patients with PFO and migraine following surgery. Notably, linoleic acid demonstrated strong diagnostic potential for this patient population. Trend analysis revealed that the levels of 3‐phenylpropionic acid and caffeine decreased on postoperative Day 3 and subsequently increased by postoperative Day 30, whereas gallic acid continuously declined. Compared to the PRE group, differential metabolites in the SM group were primarily associated with α‐linolenic acid metabolism, niacin and nicotinamide metabolism, sphingolipid signaling, and tyrosine metabolism. In contrast, differential metabolites in the POST_3d group were predominantly enriched in phenylalanine metabolism, niacin and nicotinamide metabolism, protein digestion and absorption, and caffeine metabolism.

Linoleic acid may serve as a potential biomarker, and the activation of inflammation and oxidative stress‐related pathways could contribute significantly to the development of complicated migraine in patients with PFO.