Identification and characterization of related substances in DTX-AI via LC-QTOF-HRMS.

10-O-4-Ketonephenyl carbamate docetaxel (DTX-AI) is a synthetic taxane compound that exerts antitumor effects by inhibiting microtubule depolymerization and promoting microtubule dimer synthesis. Owing to the poor water solubility of DTX-AI, the liposomal formulation for injection was developed and prepared. In vitro experiments showed that DTX-AI and its liposomal formulation outperformed DTX in terms of antitumor efficacy at much lower concentrations, with correspondingly lower toxicity.

Targeted screening and profiling of massive components of colistimethate sodium by two-dimensional-liquid chromatography-mass spectrometry based on self-constructed compound database.

In-depth study of the components of polymyxins is the key to controlling the quality of this class of antibiotics. Similarities and variations of components present significant analytical challenges. A two-dimensional (2D) liquid chromatography-mass spectrometr (LC-MS) method was established for screening and comprehensive profiling of compositions of the antibiotic colistimethate sodium (CMS).

Alzheimer's disease-like pathology induced by in middle-aged mice is mediated by NLRP3 inflammasome via the microbiota-gut-brain axis.

Background: () has been found to enter the brain and induce inflammation, contributing to Alzheimer's disease (AD). is also closely linked to gut dysbiosis. However, does induce AD-like pathology through the microbiota-gut-brain axis? There is limited literature on this topic.

Chronic Sleep Deprivation Altered the Expression of Memory-Related Genes and Caused Cognitive Memory Dysfunction in Mice.

Lack of sleep, whether acute or chronic, is quite common and negatively affects an individual's memory and cognitive function. The question of whether chronic sleep deprivation (CSD) causes cognitive impairment to arise and progress is not well studied. To investigate the effects of CSD on memory and cognition, this study began by establishing a CSD mouse model.

Pharmacovigilance of drug-drug interactions: A pharmacokinetic study on the combined oral administration of lurasidone and clozapine in rats by using LC-MS/MS.

In recent years, the expanding array of psychotropic medications has led to an increase in drug-drug interactions, particularly with combinations of different antipsychotics or psychotropic medications in clinical practice. However, the potential pharmacokinetic interactions between Lurasidone and Clozapine have not been extensively studied. Thus, this study aims to investigate these potential interactions by analyzing their pharmacokinetics in rat plasma after single oral administrations using developed LC-MS/MS methods.

In vitro and in vivo metabolic study of three new psychoactive β-keto-arylcyclohexylamines.

Since the 2000s, an increasing number of new psychoactive substances have appeared on the illicit drug market. β-Keto-arylcyclohexylamine compounds play important pharmacological roles in anesthesia; however, because these new psychoactive substances have rapidly increasing illicit recreational use, the lack of detailed toxicity data are of particular concern. Therefore, analysis of their metabolites can help forensic personnel provide references and suggestions on whether a suspect has taken an illicit new psychoactive β-keto-arylcyclohexylamine.

Metabolism of ADB-FUBIATA in zebrafish and pooled human liver microsomes investigated by liquid chromatography-high-resolution mass spectrometry.

Rationale: ADB-FUBIATA is one of the most recently identified new psychoactive substance (NPS) of synthetic cannabinoids. The co-use of in vitro (human liver microsomes) and in vivo (zebrafish) models offers abundant metabolites and may give a deep insight into the metabolism of NPS.

Methods: In vivo and in vitro metabolic studies of new synthetic cannabinoid ADB-FUBIATA were carried out using zebrafish and pooled human liver microsome models.

Kelp as a biomonitor of persistent organic pollutants in coastal areas of China: Contamination levels and human health risk.

Kelp, the brown alga distributed in coastal areas all over the world, is also an important medicine food homology product in China. However, the levels and profiles of persistent organic pollutants (POPs) in kelp have not been thoroughly investigated to date. Polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers (PBDEs) and emerging bromine flame retardants (eBFRs) were evaluated in 41 kelp samples from the main kelp producing areas in China.

Health risk assessment for human mercury exposure from Cinnabaris-containing Baizi Yangxin Pills in healthy volunteers Po administration.

Background: Cinnabaris (α-HgS), a mineral traditional Chinese material medica, has been used in combination with other herbs manifesting some definite therapeutic effects for thousands of years. But the currently reported mercury poisoning incidents raised the doubts about the safety of Cinnabaris-containing traditional Chinese medicines (TCMs). Baizi Yangxin Pills (BZYXP) is a Cinnabaris-containing TCM widely used in clinical practice.

Compatibility Study of Peptide and Glycerol Using Chromatographic and Spectroscopic Techniques: Application to a Novel Antimicrobial Peptide Cbf-14 Gel.

The interactions between active pharmaceutical ingredients (APIs) and excipients may lead to API degradation, thereby affecting the safety and efficacy of drug products. Cbf-14 is a synthetic peptide derived from Cathelicidin-BF, showing potential for bacterial and fungal infections. In order to assess impurities in Cbf-14 gel, we developed a two-dimensional liquid chromatography coupled with quadrupole/time-of-flight mass spectrometric method.

Identification of degradation products of brivaracetam using liquid chromatography quadrupole time-of-flight tandem mass spectrometry: Degradation pathway elucidation.

Rationale: Pyrrolidone-based drugs find widespread use in treating conditions such as epilepsy and Alzheimer's disease, and in various other medical applications. Brivaracetam, the latest generation of pyrrolidone drugs, has exhibited significant promise owing to chemical structure modifications. Its affinity to the SV2A receptor is double that of the previous-generation drug, levetiracetam.

Evaluation of pharmacological and pharmacokinetic herb-drug interaction between irinotecan hydrochloride injection and Kangai injection in colorectal tumor-bearing mice and healthy rats.

Kangai (KA) injection, a Chinese herbal injection, is often used in combination with irinotecan (CPT-11) to enhance the effectiveness of anti-colorectal cancer treatment and alleviate side effects. However, the combined administration of this herb-drug pair remains controversial due to limited pre-clinical evidence and safety concerns. This study aimed to determine the pre-clinical herb-drug interactions between CPT-11 and KA injection to provide a reference for their clinical co-administration.

Metabolite characterisation of the peptide-drug conjugate LN005 in liver S9s by UHPLC-Orbitrap-HRMS.

LN005 is a peptide-drug conjugate (PDC) targeting glucose-regulated protein 78 (GRP78) to treat several types of cancer, such as breast, colon, and prostate cancer.As a new drug modality, understanding its metabolism and elimination pathways will help us to have a whole picture of it. Currently, there are no metabolic studies on LN005; therefore, this study aimed to investigate the metabolism of LN005, clarify its metabolic profile in the liver S9s of different species, and identify the major metabolic pathways and differences between species.

Metabolism investigation of the peptide-drug conjugate LN005 in rats using UHPLCHRMS.

LN005, as a peptide-drug conjugate (PDC), is a conjugate of the homing peptide VAP and doxorubicin (DOX). The exceptional targeting ability of the homing peptide VAP is directed toward glucose-regulated protein (GRP78), a highly expressed protein primarily found in the endoplasmic reticulum of various solid tumors. However, there are limited reports regarding the metabolism of peptide-drug conjugates (PDCs), and the in vivo metabolism of LN005 has yet to be investigated.

Separation and characterization of related substances of Lurasidone hydrochloride by LC-QTOF-MS techniques.

In the present study, a reliable LC-QTOF-MS method was developed and employed for the separation and characterization of process-related substances and forced degradation products of Lurasidone hydrochloride. The chromatographic separation was carried out using an Agilent Poroshell 120 Bonus-RP C18 column (100 mm × 4.6 mm, 2.

Gemcitabine enhances pharmacokinetic exposure of the major components of Danggui Buxue Decoction in rat via the promotion of intestinal permeability and down-regulation of CYP3A for combination treatment of non-small cell lung cancer.

Context: Danggui Buxue Decoction (DBD), a traditional Chinese medicine formula, has the potential to enhance the antitumor effect of gemcitabine in non-small cell lung cancer (NSCLC) treatment by increasing gemcitabine's active metabolites. However, whether gemcitabine affects the pharmacokinetics of DBD's major components remains unclear.

Objective: This study evaluates the herb-drug interaction between DBD's major components and gemcitabine and validates the underlying pharmacokinetic mechanism.

Preclinical PK investigation of a novel IDO1/TDO dual inhibitor-SHR9146 in mouse plasma and tissues by LC-MS/MS.

Purpose: The aim of the present study was to establish a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the determination of SHR9146, a novel IDO1/TDO dual inhibitor, in mouse plasma and tissues, and to apply it to investigate the preclinical plasma pharmacokinetics and tissue distribution of SHR9146 in mice.

Methods: Samples were spiked with deuterated SHR9146-d as an internal standard and pretreated by protein-precipitation extraction with methanol. Chromatographic separation was performed on a Venusil ABS C18 column (150 × 4.

Crude polysaccharide from Danggui Buxue decoction enhanced the anti-tumor effect of gemcitabine by remodeling tumor-associated macrophages.

Tumor-associated macrophages (TAMs) with an M2-phenotype mediate gemcitabine resistance to cancer by influencing the metabolic enzymes of gemcitabine and releasing competitive deoxycytidine (dC). Our previous studies showed that Danggui Buxue Decoction (DBD), a traditional Chinese medicinal recipe, enhances the anti-tumor activity of gemcitabine in vivo and alleviates gemcitabine-induced myelosuppression. However, the material basis and exact mechanism underlying its enhanced effects remain unclear.

In vitro and in vivo metabolism of 3-Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography-high-resolution mass spectrometry.

3-Methoxyeticyclidine (3-MeO-PCE), a phencyclidine-type substance, has a higher N-methyl-D-aspartate receptor binding affinity than phencyclidine and an involvement in fatal intoxication cases. The aim of this study was to identify new biomarkers and biotransformation pathways for 3-MeO-PCE. In vitro models were established using zebrafish and human liver microsomes for analysis of the phases I and II metabolites of 3-MeO-PCE by liquid chromatography-high-resolution mass spectrometry.

Application of the metal ions as potential population biomarkers for wastewater-based epidemiology: estimating tobacco consumption in Southern China.

Wastewater-based epidemiology (WBE) is an objective approach for the estimation of population-level exposure to a wide range of substances, in which the use of a population biomarker (PB) could significantly reduce back-calculation errors. Although some endogenous or exogenous compounds such as cotinine and other hormones have been developed as PBs, more PBs still need to be identified and evaluated. This study aimed to propose a novel method to estimate population parameters from the mass load of metal ion biomarkers in wastewater, and estimate the consumption of tobacco in 24 cities in Southern China using the developed method.

Development of an ELISA Assay for the Determination of SARS-CoV-2 Protein Subunit Vaccine Antigen Content.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) protein subunit vaccine is one of the mainstream technology platforms for the development of COVID-19 vaccines, and most R&D units use the receptor-binding domain (RBD) or spike (S) protein as the main target antigen. The complexity of vaccine design, sequence, and expression systems makes it urgent to establish common antigen assays to facilitate vaccine development. In this study, we report the development of a double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) to determine the antigen content of SARS-CoV-2 protein subunit vaccines based on the United States Pharmacopeia <1220> and ICH (international conference on harmonization) Q14 and Q2 (R2) requirements.

Hepatotoxic metabolites in - Comparative toxicology in mice.

(PM) and (rhubarb) contain similar hepatocyte-toxic anthraquinones such as emodin (major free anthraquinone in PM), physcion and their glycosides. In clinical practice, PM hepatotoxicity has been widely reported, although rhubarb is not recognized as hepatotoxic. To clarify the substances basis (key components) of PM hepatotoxicity, based on the characteristic components' similarity within PM, rhubarb and their concocted forms, a comparative sub-acute toxicity study was designed in mice.

Pharmacovigilance of Herb-Drug Interactions: A Pharmacokinetic Study on the Combined Administration of Tripterygium Glycosides Tablets and Leflunomide Tablets in Rats by LC-MS/MS.

A popular and widely used combination therapy of leflunomide (LEF) and Tripterygium glycosides tablets (TGTS) has become a valuable clinical tool in China for the treatment of rheumatoid arthritis. This regimen has not been evaluated either in terms of interaction or toxicity, even given the rising concerns about LEF’s prolonged elimination half-life and TGT’s narrow therapeutic index, in addition to the current trend of using high doses of LEF. Thus, this study determines the potential adverse drug reactions between these two medicines.

Simultaneous determination of nirmatrelvir and ritonavir in human plasma using LC-MS/MS and its pharmacokinetic application in healthy Chinese volunteers.

Paxlovid, a copackaged medication of nirmatrelvir tablets (150 mg) and ritonavir tablets (100 mg) developed by Pfizer, is one of the first orally accessible COVID-19 antiviral medicines to be approved for emergency usage. In this research, an efficient LC-MS/MS method for simultaneous determination of nirmatrelvir and ritonavir in human plasma was established and validated with remdesivir as an internal standard. Chromatographic separations were carried out on a Thermo BDS Hypersil C18 column (4.