Development of a Novel Immunoprecipitation Method for Extracting Monoclonal Antibodies From Brain Tissue and Its Application to Assessing In Vivo Brain Penetration in Mouse via Liquid Chromatography-Mass Spectrometry.

A novel extraction method was developed to quantify monoclonal antibodies from brain tissue, crucial for pharmacokinetic assessments. We focused on optimizing detergent use for compatibility with liquid chromatography-mass spectrometry analysis. IGEPAL and sodium deoxycholate were selected for their ability to preserve antibody integrity during extraction, with conditions optimized to a 4% concentration.

Quantification of Methylene Blue and Evaluation of Its Pharmacokinetics in ICR Mice by Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometry Using Difluoroacetic Acid.

Methylene blue (MB), a phenothiazine derivative, is currently under clinical trials for Alzheimer's disease (AD) due to its potential to inhibit tau aggregation, a key pathological process in AD. In this study, we developed and qualified a rapid and reliable liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF-MS) method for the quantification of MB in mouse plasma and brain samples. Chromatographic separation was achieved using a PolymerX RP-1 100 Å (50 × 2 mm, 5 μm) column with a mobile phase consisting of water and methanol containing 0.

High-Performance Nickel-Bismuth Oxide Electrocatalysts Applicable to Both the HER and OER in Alkaline Water Electrolysis.

As an electrocatalyst for water electrolysis, nickel oxide (NiO) has received significant attention due to its cost-effectiveness and high reactivity among non-noble-metal-based catalytic materials. However, NiO still exhibits poor alkaline hydrogen evolution reaction (HER) and oxygen evolution reaction (OER) kinetics compared to conventional noble metal-based catalysts. This is because NiO has a strong interaction with protons for the HER and too low free energy of the OH* state, resulting in slower rate-determining step (RDS) kinetics for the OER.

Investigation of pharmacokinetic properties of a PEGylated bilirubin nanoparticle in male Sprague-Dawley rats using liquid chromatography-quadrupole time-of-flight mass spectrometry.

Polyethylene glycol (PEG) was introduced into synthetic bilirubin 3α and a PEGylated bilirubin 3α nanoparticle (BX-001N, Brixelle®) was developed for the first time.An microsomal stability study, in vivo PK studies with intravenous bolus (IV) and subcutaneous injection (SC), and a semi-mass balance study of BX-001N were investigated to evaluate its pharmacokinetic (PK) properties in male Sprague-Dawley (SD) rats using developed liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-qTOF/MS).Following IV administration at 10 or 30 mg/kg, BX-001N showed very low clearance (0.

Evaluation of In Vivo Prepared Albumin-Drug Conjugate Using Immunoprecipitation Linked LC-MS Assay and Its Application to Mouse Pharmacokinetic Study.

There have been many attempts in pharmaceutical industries and academia to improve the pharmacokinetic characteristics of anti-tumor small-molecule drugs by conjugating them with large molecules, such as monoclonal antibodies, called ADCs. In this context, albumin, one of the most abundant proteins in the blood, has also been proposed as a large molecule to be conjugated with anti-cancer small-molecule drugs. The half-life of albumin is 3 weeks in humans, and its distribution to tumors is higher than in normal tissues.

Investigation of In Vitro and In Vivo Metabolism of α-Amanitin in Rats Using Liquid Chromatography-Quadrupole Time-of-Flight Mass Spectrometric Method.

The purpose of this study is to investigate the difference of in vitro-in vivo correlation of α-amanitin from clearance perspectives as well as to explore the possibility of extra-hepatic metabolism of α-amanitin. First, a liquid chromatography-quadrupole-time-of-flight-mass spectrometric (LC-qTOF-MS) method for α-amanitin in rat plasma was developed and applied to evaluate the in vitro liver microsomal metabolic stability using rat and human liver microsomes and the pharmacokinetics of α-amanitin in rat. The predicted hepatic clearance of α-amanitin in rat liver microsomes was quite low (5.

Quantitative Analysis of Daporinad (FK866) and Its In Vitro and In Vivo Metabolite Identification Using Liquid Chromatography-Quadrupole-Time-of-Flight Mass Spectrometry.

Daporinad (FK866) is one of the highly specific inhibitors of nicotinamide phosphoribosyl transferase (NAMPT) and known to have its unique mechanism of action that induces the tumor cell apoptosis. In this study, a simple and sensitive liquid chromatography-quadrupole-time-of-flight-mass spectrometric (LC-qTOF-MS) assay has been developed for the evaluation of drug metabolism and pharmacokinetics (DMPK) properties of Daporinad in mice. A simple protein precipitation method using acetonitrile (ACN) was used for the sample preparation and the pre-treated samples were separated by a C18 column.

Suggestion of Safety Certification Standards and Performance Evaluation Methods for Fabricated Mobile Scaffold in South Korea.

At construction sites, various types of temporary equipment and structures are used for safety and work efficiency. However, various temporary equipment-related accidents frequently occur for many reasons, including inappropriate installation, usage, and material and structural imperfections. A mobile scaffold is one of the most commonly used indoor temporary equipment for work in high places.

Assessments of the In Vitro and In Vivo Linker Stability and Catabolic Fate for the Ortho Hydroxy-Protected Aryl Sulfate Linker by Immuno-Affinity Capture Liquid Chromatography Quadrupole Time-of-Flight Mass Spectrometric Assay.

Antibody-drug conjugate (ADC) linkers play an important role in determining the safety and efficacy of ADC. The Ortho Hydroxy-Protected Aryl Sulfate (OHPAS) linker is a newly developed linker in the form of a di-aryl sulfate structure consisting of phenolic payload and self-immolative group (SIG). In this study, using two bioanalytical approaches (namely "bottom-up" and "middle-up" approaches) via the liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method, in vitro and in vivo linker stability experiments were conducted for the OHPAS linker.

Qualification and application of liquid chromatography-quadrupole time-of-flight mass spectrometric method for the determination of carisbamate in rat plasma and prediction of its human pharmacokinetics using physiologically based pharmacokinetic modeling.

Carisbamate is an antiepileptic drug and it also has broad neuroprotective activity and anticonvulsant reaction. In this study, a liquid chromatography-quadrupole time-of-flight mass spectrometric (LC-qTOF-MS) method was developed and applied for the determination of carisbamate in rat plasma to support and studies. A quadratic regression (weighted 1/concentration), with an equation y = ax + bx + c, was used to fit calibration curves over the concentration range from 9.

Assessment of Pharmacokinetics and Metabolism Profiles of SCH 58261 in Rats Using Liquid Chromatography-Mass Spectrometric Method.

5-Amino-7-(2-phenylethyl)-2-(2-furyl)-pyrazolo(4,3-e)-1,2,4-triazolo(1,5-c) pyrimidine (SCH 58261) is one of the new chemical entities that has been developed as an adenosine A receptor antagonist. Although SCH 58261 has been reported to be beneficial, there is little information about SCH 58261 from a drug metabolism or pharmacokinetics perspective. This study describes the metabolism and pharmacokinetic properties of SCH 58261 in order to understand its behaviors in vivo.

In Vitro, In Silico, and In Vivo Assessments of Pharmacokinetic Properties of ZM241385.

Parkinson's disease is one of the most common neurodegenerative diseases. Adenosine regulates the response to other neurotransmitters in the brain regions related to motor function. In the several subtypes of adenosine receptors, especially, adenosine 2A receptors (ARs) are involved in neurodegenerative conditions.

Prenatal development toxicity study of zinc oxide nanoparticles in rats.

This study investigated the potential adverse effects of zinc oxide nanoparticles ([ZnO(SM20(+)) NPs] zinc oxide nanoparticles, positively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague-Dawley rats. ZnO(SM20(+)) NPs were administered to pregnant rats by gavage at 0, 100, 200, and 400 mg/kg/day. All dams were subjected to a cesarean section on gestational day 20, and all of the fetuses were examined for external, visceral, and skeletal alterations.

Effect of zinc oxide nanoparticles on dams and embryo-fetal development in rats.

This study investigated the potential adverse effects of zinc oxide nanoparticles (ZnO(SM20[-]) NPs; negatively charged, 20 nm) on pregnant dams and embryo-fetal development after maternal exposure over the period of gestational days 5-19 with Sprague Dawley rats. ZnO(SM20(-)) NPs were administered to pregnant rats by gavage at 0 mg/kg/day, 100 mg/kg/day, 200 mg/kg/day, and 400 mg/kg/day. All dams were subjected to caesarean section on gestational day 20, and all the fetuses were examined for external, visceral, and skeletal alterations.

Dose-response effects of diphenylhydantoin on pregnant dams and embryo-fetal development in rats.

Despite the widespread use of diphenylhydantoin (DPH), there is a lack of reliable information on the teratogenic effects, correlation with maternal and developmental toxicity, and dose-response relationship of DPH. This study investigated the dose-response effects of DPH on pregnant dams and embryo-fetal development as well as the relationship between maternal and developmental toxicity. DPH was orally administered to pregnant rats from gestational days 6 through 15 at 0, 50, 150, and 300 mg/kg/day.

Spermatotoxic effects of α-chlorohydrin in rats.

This study was conducted to investigate the potential effects of α-chlorohydrin (ACH) on epididymal function and antioxidant system in male rats. The test chemical was administered to male rats by gavage at doses of 0, 3, 10, and 30 mg/kg/day for 7 days. Twenty-four male rats were randomly assigned to four experimental groups, with six rats in each group.

Evaluation of Maternal Toxicity in Rats Exposed to Multi-Wall Carbon Nanotubes during Pregnancy.

Objectives: The present study investigated the potential adverse effects of multi-wall carbon nanotubes (MWCNTs) on pregnant dams and embryonic development following maternal exposure in rats.

Methods: MWCNTs were orally administered to pregnant rats from gestational day (GD) 6 through 19 at dose levels of 0, 8, 40, 200, and 1000 mg/kg/day. During the test period, clinical signs, mortality, body weights, food consumption, serum biochemistry, oxidant-antioxidant status, gross findings, organ weights, and Caesarean section findings were examined.

Protective effects of pine bark extract on developmental toxicity of cyclophosphamide in rats.

This study investigated the protective effects of pine bark extract (Pycnogenol®, PYC) against cyclophosphamide (CP)-induced developmental toxicity in rats. A total of 44 mated females were randomly assigned to the following four experimental groups: (1) vehicle control, (2) CP, (3) CP&PYC, or (4) PYC. All dams were subjected to a Caesarean section on day 20 of gestation, and fetuses were examined for morphological abnormalities.

Effects of melamine on pregnant dams and embryo-fetal development in rats.

There are worldwide concerns regarding the potential adverse effect of melamine. This study investigated the potential effects of melamine on pregnant dams and embryo-fetal development in Sprague-Dawley rats following maternal exposure on gestational days (GD) 6-20. Melamine was administered to pregnant rats by gavage at doses of 0, 200, 400 and 800 mg kg⁻¹ per day (n = 8-10 for each group).

Maternal exposure to multi-wall carbon nanotubes does not induce embryo-fetal developmental toxicity in rats.

Background: Although the potential risk of carbon nanotubes (CNTs) to humans has recently increased due to expanding production and widespread use, the potential adverse effects of CNTs on embryo-fetal development have not yet been determined.

Methods: This study investigated the potential effects of multi-wall CNTs (MWCNTs) on pregnant dams and embryo-fetal development in rats. MWCNTs were administered to pregnant rats by gavage at 0, 40, 200, and 1,000 mg/kg/day.

Induction of oxidative stress in the epididymis of rats after subchronic exposure to epichlorohydrin.

This study investigated the effects of epichlorohydrin (ECH) on spermatogenesis and antioxidant system in rats. An increase in the incidence of clinical signs, gross pathology and histopathology findings in the epididymidis, and sperm abnormalities and a decrease in the testicular spermatid counts, epididymal sperm counts, and sperm motility were observed at 30 mg/kg/day. Oxidative stress in the epididymal tissue was detected at > or =3.

Reproductive and developmental toxicity of amitraz in sprague-dawley rats.

The present study was conducted to obtain information on the effects of amitraz on reproductive and developmental parameters in rats. The test chemical was administered via the drinking water containing 0, 40, 120, and 360 ppm to male rats from 2 weeks before mating to the end of 14-day mating period and to females from 2 weeks before mating, throughout mating, gestation and up to lactational day 4. During the study period, clinical signs, body weights, food intake, organ weights, reproductive and littering findings, necropsy findings, sperm parameters, and histopathology were examined.

Effects of Concrete and Wood Building Environments on Pregnant Dams and Embryo-Fetal Development in Rats.

We have recently reported that the continuous exposure of rats to a concrete building environment under cool temperatures had adverse effects on general health parameters and embryo-fetal development. This study examined to compare the potential effects of concrete and wood building environments on pregnant dams and embryo-fetal development in rats. Groups of 10 mated females were exposed to polycarbonate (control), concrete, or wood cages from gestational days (GD) 0 to 20 under cool temperatures (11.

Dose-Response Effects of Epichlorohydrin on Male Reproductive Function in Rats.

Present study was conducted to investigate potential effects of epichlorohydrin on testicular and epididymal function in male rats. The test chemical was administered to adult male rats by gavage at dose levels of 0, 3.125, 12.