In this study, we investigate the metabolic profile of strychnine in human urine following controlled administration using liquid chromatography-quadrupole-Orbitrap mass spectrometry. A total of 25 metabolites were characterized and identified. These included 21 previously unreported and 4 previously reported metabolites. Four unreported metabolic pathways were discovered, namely, reduction, methylation, glycosylation, and glucuronidation. Among these, hydroxylation was identified as the major metabolic pathway. The detection windows in the urine for all 25 metabolites were compared with that of the parent drug. Metabolite S10 (2,3-dimethoxy-strychnine) was proposed as a novel potential biomarker for strychnine misuse, rather than strychnine itself, due to its longer detection time and higher number of strychnine-positive time points (exceeding 50 ng/mL in human urine) compared to the parent compound after oral administration. The identification of S10 extends the detection window and offers critical insights for doping control applications.

Lung injury is one of the most common clinical respiratory diseases, caused by the exposure of lung tissue to various stimuli (including hypoxia, ischemia-reperfusion, and foreign substances). Among them, chronic lung injury is characterized by continuous inflammation in the lungs, which damages the endothelial and epithelial cell barriers within the lungs. Clinically, it presents as severe hypoxia and diffuse functional impairment, and on imaging, it shows diffuse alveolar damage, accompanied by varying degrees of inflammation and airway obstruction. Several studies have highlighted the role of gut microbiota in modulating immune responses and pathological features of respiratory diseases through the gut-lung axis. However, the precise metabolic mechanism remains unknown. A lung injury model was generated by transplanting microbiota from acute lung injury (ALI) patients into healthy C57BL/6J mice. The changes in the gut microbiota and metabolic phenotypes of the feces samples from ALI patients and lung-injured mice were analyzed using 16S rRNA sequencing technology and metabolomics based on 1H-nuclear magnetic resonance (1H-NMR), respectively. The effect of gut microbiota on lung injury was also explored after giving an oral vancomycin treatment to lung-injury mice. The data presented here show that Firmicutes formed the vital species of microbiota that was different in lung-injury mice. Moreover, butyrate (produced by Firmicutes) was the most crucial metabolite in the feces samples of ALI patients and lung-injury mice. ELISA and Hematoxylin-Eosin results showed aggravated functional disturbances in the intestinal barrier of ALI patients and lung inflammation in the lung-injured mice. These phenomena were significantly alleviated after the oral administration of vancomycin. Besides, the utilization of butyrate in the colon of mice was increased considerably. Thus, vancomycin can affect the metabolism of butyrate in the colon by influencing the intestinal microbiota, and it can help in the treatment of lung injury.

Impact of oral iron dosing regimens on iron biomarkers during pregnancy: insights from the PANDA trial.

Restoring immunoglobulin A/polymeric immunoglobulin receptor transport axis for the oral treatment of inflammatory bowel disease.

Dairy industry side-stream lactose as a surrogate for commercial products during major supply disruptions.

Cistanoside A (Cis A) has received more attention because of its potential in the treatment of osteoporosis. However, its invivo process remains unknown. In this study, a simple liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of cistanoside A in rat plasma, urine, and feces. After prepared by protein precipitation, cistanoside A and IS were separated on a Waters BEH C18 column with MS detection operated in positive multiple reaction monitoring mode. The method was fully validated and applied to the pharmacokinetic and excretion studies of cistanoside A in rats after intravenous (5 mg/kg) and oral (10, 20, and 40 mg/kg) administration. After intravenous administration, cistanoside A showed moderate clearance (0.52 ± 0.04 L*h/kg), low volume of distribution, and short terminal half-life (0.43 ± 0.03 h). After oral administration at doses of 10, 20, and 40 mg/kg, the system exposure increased lower than the increase of dose, and the oral bioavailabilities were 0.39%, 0.38%, and 0.23%, respectively. After oral administration, the average cumulative excretion rate was 0.03% in urine and 1.62% in feces at 24 h. In summary, this study defined the pharmacokinetic and excretion characteristics of cistanoside A in rats, which could provide useful information for its further development.

Hypaphorine is an indole alkaloid from Erythrina velutina, which exerts excellent anti-inflammatory and antioxidant properties. In this study, a simple liquid chromatography tandem mass spectrometry (LC-MS/MS) method was developed and validated for the determination of hypaphorine in rat plasma, urine, and feces. After acetonitrile-mediated protein precipitation, hypaphorine, and IS were separated on a C18 column with MS detection operated in positive multiple reaction monitoring mode. The method was fully validated and applied to the pharmacokinetic and excretion studies of hypaphorine in rats after intravenous (1 mg/kg) and oral (5, 10, and 20 mg/kg) administration. After administration, hypaphorine showed low clearance (0.31 ± 0.06 L*h/kg), moderate volume of distribution, and moderate terminal half-life (5.61-7.33 h). After oral administration at doses of 5, 10, and 20 mg/kg, the system exposure increased slightly lower than the increase of dose, and the oral bioavailability values were 29.19%, 25.72%, and 20.06%, respectively. After intravenous administration, the cumulative excretion rate of hypaphorine was 25.80% in urine and 0.60% in feces. After oral administration, the cumulative excretion rate of hypaphorine was 8.22% in urine and 16.60% in feces at 48 h. In summary, this study defined the pharmacokinetic and excretion characteristics of hypaphorine in rats, which could provide useful information for its further development.

Oral administration of (S)-ketamine for treatment-resistant depression (TRD), as alternative to the registered intranasal or off-label intravenous administrations, has high potential. However, it is characterized by an extensive first-pass metabolism, resulting in low (S)-ketamine exposure and high levels of active metabolites, including (S)-norketamine and (S)-hydroxynorketamine. The relative contribution of the parent and metabolites to the resulting antidepressant effects remains unclear. Therefore, this study aimed to first characterize the pharmacokinetics (PK) of (S)-ketamine and its metabolites after oral and intravenous administration in healthy participants and secondly quantify the pharmacokinetic/pharmacodynamic (PKPD) relationship of (S)-ketamine and (S)-norketamine to the subjective effects measured on the visual analogue scale (VAS) 'Feeling High'. Data from a previously conducted clinical study was used, where 17 healthy participants received oral (0.20 and 0.45 mg/kg) and intravenous (0.4mg/kg over 40 min) (S)-ketamine in a randomized, placebo-controlled, crossover clinical trial. A semi-physiological population PK model was developed to describe the first-pass metabolism and (S)-ketamine and subsequently (S)-norketamine concentrations were linked to the VAS 'Feeling High' using a bounded integer modelling approach. A significant (S)-norketamine PKPD relationship was determined alongside (S)-ketamine, but estimated variance of the bounded integer model was high warranting further investigation. Our analysis suggests that not (S)-ketamine, but its metabolite, is the main driver of subjective effects after oral administration, and as such may also contribute to antidepressant effects in TRD patients receiving oral (S)-ketamine.

An oral-to-urinalysis fluorescent prodrug platform for IBD theranostics.

In vivo biotransformation and metabolic profiling of dimyricetin-yl-diselenide (DMS), a structurally defined organoselenium flavonoid, in rats after oral and subcutaneous administration by UHPLC-HRMS.

Compound Shougong Powder (CSP) is composed of six Chinese herbal medicines and exerts effects in reducing swelling and relieving pain. It is mainly applied in clinical practice as an adjuvant therapy for various malignant tumors; however, its chemical constituents and the material basis of its efficacy have not been fully clarified. This study aimed to clarify the chemical constituents, their migration and distribution invivo, and the pharmacodynamic material basis and anti-tumor mechanism of CSP. Ultrahigh-performance liquid chromatography (UHPLC) combined with high-resolution mass spectrometry (HRMS) was employed to identify the chemical constituents of CSP and their migration and distribution in mouse serum and tissues; network pharmacology was integrated to explore the potential anti-tumor mechanism of the stably distributed constituents. A total of 3645 chemical constituents were identified under both positive- and negative-ion modes. Following oral administration, 611 constituents derived from the formulation were detected in mouse serum. In tissues, 1187, 1020, 618, and 401 prototype constituents were identified in the stomach, esophagus, liver, and lungs, respectively. Systematic analysis of all identified constituents revealed 95 that were stably distributed across the original formulation, serum, and the liver, lung, esophagus, and stomach. These 95 constituents stably present in the formula, serum, and target tissues may act synergistically to contribute to the antitumor and analgesic efficacy of CSP. Furthermore, network pharmacology was integrated to explore the potential mechanism of these constituents. A total of 152 overlapping targets between CSP and cancer were identified by Venn diagram analysis. Protein-protein interaction (PPI) network analysis revealed hub genes such as ALB, PTGS2, EGFR, CXCL8, and GSK3B. Gene Ontology (GO) enrichment showed involvement in apoptotic regulation, cell proliferation, and kinase activity, while Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis highlighted key pathways including cancer, PI3K-Akt, TNF, and MAPK signaling pathways. These findings clarify the chemical constituents and invivo distribution of CSP, confirm that the 95 stably distributed constituents are the potential pharmacodynamic material basis, and suggest that CSP exerts anti-tumor effects through a multicomponent, multi-target, and multi-pathway regulatory network, providing a basis for further investigation into the pharmacodynamic material foundation of CSP in the treatment of malignant tumors.

Microparticle-based drug delivery systems have gained widespread recognition for their ability to enable sustained drug release. However, their utility in oral administration has been constrained by suboptimal gastrointestinal retention. This study systematically evaluated how engineered microparticle morphology and surface topography influence intestinal adhesion dynamics and drug release profiles. Through controlled modulation of surface roughness and particle geometry, we demonstrated that non-spherical architectures, particularly waterdrop-like microparticles (WDMPs), exhibited superior mucoadhesive properties, achieving 1.25-fold prolonged gastrointestinal retention time while maintaining optimal drug release kinetics (71.2% cumulative release over 10 h). In a murine inflammatory bowel disease (IBD) model, dexamethasone (DXM)-loaded WDMPs outperformed conventional free drug administration, manifesting in significantly improved therapeutic outcomes: 1.16-fold enhanced weight recovery, 1.27-fold greater colon length preservation, and superior histopathological scores. Notably, WDMPs also boosted oral bioavailability of micronutrients by 1.2-to-1.6-fold, highlighting its dual applicability for both pharmaceutical and nutraceutical delivery. These comprehensive findings positioned WDMPs as a transformative oral delivery platform that addresses longstanding challenges in gastrointestinal drug absorption, offering substantial potential for clinical translation. STATEMENT OF SIGNIFICANCE: This study demonstrates the potential of engineered microparticle morphology to address key challenges in oral drug delivery. By investigating the effects of particle morphology and surface topography on intestinal retention and drug release, we show that non-spherical, rough microparticles exhibit enhanced mucoadhesion and sustained drug release. Waterdrop-like Microparticles (WDMPs) provide a significant improvement in gastrointestinal retention and drug release kinetics. WDMPs also outperform free dexamethasone in a murine model of inflammatory bowel disease. Additionally, WDMPs enhance oral bioavailability for micronutrients, offering dual-purpose potential for pharmaceutical and nutraceutical applications. These findings highlight the critical role of microparticle morphology in optimizing drug delivery efficiency and underscore the versatility of WDMPs as a customizable platform for controlled release therapies.

Systematic characterization of chemical constituents and in vivo metabolites of Jiuwei Qianghuo Granules by UPLC-Q-TOF-MS/MS.

Structure-guided engineering of serratiopeptidase using constant-pH molecular dynamics and site-directed mutagenesis to improve pH-dependent functional resilience.

Protective effects of topical and oral Ganoderma lucidum extracts against ultraviolet B-induced cataract development and chemical ocular surface injury in a rat model.

A highly specific and sensitive UPLC-MS/MS assay was established and validated for simultaneous determination of bullatine A and bullatolide B in rat plasma. Midazolam was employed as the internal standard (IS). Separation was performed on a Waters UPLC BEH C18 column using a gradient mobile phase consisting of methanol and 0.1% aqueous formic acid. Detection was carried out in the mode of multiple reaction monitoring (MRM), m/z 344.3 → 105.0 (bullatine A), m/z 438.6 → 154.2 (bullatine B), and m/z 326.2 → 291.4 (IS). Plasma proteins were effectively precipitated with acetonitrile prior to analysis. Good linear calibration curves (r2 > 0.995) were obtained in a range of 0.5-600 ng/mL for both analytes, with a limit of quantification of 0.5 ng/mL. Both intra- and inter-day precision (percent RSD) were less than 14% for bullatine A and less than 13% for bullatine B. Accuracy (percentage nominal concentration) was within the range of 91%-109% for all quality control levels. The proposed method exhibited excellent sensitivity and selectivity and was successfully applied to compare the pharmacokinetics following intravenous and oral administration in rats. The absolute oral bioavailability was determined to be 4.3% for bullatine A and 12.8% for bullatine B.

A comprehensive study on enrofloxacin residue depletion in five chicken breeds.

Cocrystal mitigates the effects of elevated gastric pH on oral absorption of weakly basic drugs: a case study with ketoconazole-succinic acid cocrystal on beagle dogs.

Isosakuranetin is a natural flavonoid containing a 4'-O-methyl group on the molecular structure and has a broad range of pharmacological activities. In this study, a sensitive and robust UPLC-ESI-MS/MS method was developed and fully validated for quantitative determination of isosakuranetin in rat plasma, enabling a comprehensive evaluation of the pharmacokinetics and oral bioavailability of isosakuranetin. Isoscoparin was the internal standard (IS). The plasma samples were prepared by protein precipitation with acetonitrile. Chromatographic separation was conducted with a BEH C18 column and a gradient mobile phase consisting of acetonitrile and 0.1% formic acid aqueous solution. The detection was accomplished in negative electrospray ionization (ESI) by multiple reaction monitoring (MRM) mode. The assay had excellent linearity (r > 0.995) in a linear concentration range of 0.5-800 ng/mL. Precision (intra- day and inter-day) was less than 13%, and extraction recovery was above 89%. Accuracy was between 91% and 113%, and the matrix effects were 93%-104%. Overall, this method was rapid, specific, reproducible, and sufficiently sensitive for invivo pharmacokinetic studies in rats. After oral administration, the absolute bioavailability of isosakuranetin was calculated to be 64.6%.

TPN729 is an oral phosphodiesterase type 5 (PDE5) inhibitor for the treatment of erectile dysfunction. Although several studies have investigated TPN729 metabolism, quantitative data delineating the involvement of primary excretion pathways and the fraction of each metabolic pathway are limited. This study utilized radioisotope tracing methods to examine the pharmacokinetics, mass balance, and metabolism of [14C]TPN729 (100 μCi) after a single oral administration of 50 mg in healthy male Chinese participants. TPN729 was rapidly absorbed, with a time to peak concentration (Tmax) of 1.58 h, suggesting that the peak plasma concentration was achieved shortly after oral administration. The elimination half-life (t1/2) in plasma was 11.3 h, indicating that the drug was eliminated from the body at a relatively slow rate. The ratio of total drug-related chemicals in whole blood to plasma was 0.613, indicating preferential distribution in plasma. Mass balance measurements revealed that 95.7% of the radiolabeled chemical was excreted 192 h after administration predominantly through feces (78.5%) rather than urine (17.2%). This study identified 17 metabolites in plasma, urine, and feces. All metabolites were phase I metabolites and were mainly generated through dealkylation and oxidation. These findings elucidate the metabolic pathway and clearance mechanisms of TPN729 in humans.