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Biomedical Chromatography : BMC Jan 2023Potential genotoxic impurities (PGI) and N-nitrosamine impurities in active pharmaceutical ingredients (APIs) and their determination at low levels are substantial...
Identification and validation of potential genotoxic impurities, 1,3-dichloro-2-propanol, and 2,3-dichloro-1-propanol, at subtle levels in a bile acid sequestrant, colesevelam hydrochloride, using hyphenated GC-MS technique.
Potential genotoxic impurities (PGI) and N-nitrosamine impurities in active pharmaceutical ingredients (APIs) and their determination at low levels are substantial challenges for cholesterol-lowering agents in recent years. Herein we developed a robust, reliable, rapid, accurate and validated technique of gas chromatography equipped with a mass spectrometer (GC-MS) for quantifying subtle levels of 1,3-dichloro-2-propanol (PGI-I) and 2,3-dichloro-1-propanol (PGI-II) in colesevelam hydrochloride drug substance (bile acid sequestrant). The separation of colesevelam hydrochloride, PGI-I and PGI-II was executed with chromatographic technique using a capillary column, DB-624 measuring with 30 m × 0.32 mm × 1.8 μm specification of 6% cyanopropylphenyl-94% dimethylpolysiloxane copolymer and helium carrier gas. This developed technique gave a good intensity peak without any interference and extra masses at the retention times of 11.17 min for PGI-I and 11.59 min for PGI-II, which was adequate, with mass spectra (m/z) of 79 and 62, respectively. The method's sensitivity and linearity are demonstrated by its detection and quantification limits at subtle levels with correlation coefficients of 0.9965 for PGI-I and 0.9910 for PGI-II. The determination is mainly focused on improving sensitivity with the limits of detection and quantitation far below the specifications, which can support tighter limits. This results in a cost-effective and easily adoptable methodology having precise and accurate results in colesevelam hydrochloride API at subtle levels.
Topics: Colesevelam Hydrochloride; Gas Chromatography-Mass Spectrometry; 1-Propanol; Propanols; Hypolipidemic Agents; DNA Damage; Bile Acids and Salts
PubMed: 36250913
DOI: 10.1002/bmc.5528 -
Inhalation Toxicology 2020The inhalation of air-borne toxicants is associated with adverse health outcomes which can be somewhat mitigated by enhancing endogenous anti-oxidant capacity. Carnosine...
OBJECTIVE
The inhalation of air-borne toxicants is associated with adverse health outcomes which can be somewhat mitigated by enhancing endogenous anti-oxidant capacity. Carnosine is a naturally occurring dipeptide (β-alanine-L-histidine), present in high abundance in skeletal and cardiac muscle. This multi-functional dipeptide has anti-oxidant properties, can buffer intracellular pH, chelate metals, and sequester aldehydes such as acrolein. Due to these chemical properties, carnosine may be protective against inhaled pollutants which can contain metals and aldehydes and can stimulate the generation of electrophiles in exposed tissues. Thus, assessment of carnosine levels, or levels of its acrolein conjugates (carnosine-propanal and carnosine-propanol) may inform on level of exposure and risk assessment.
METHODS
We used established mass spectroscopy methods to measure levels of urinary carnosine ( = 605) and its conjugates with acrolein ( = 561) in a subset of participants in the Louisville Healthy Heart Study (mean age = 51 ± 10; 52% male). We then determined associations between these measures and air pollution exposure and smoking behavior using statistical modeling approaches.
RESULTS
We found that higher levels of non-conjugated carnosine, carnosine-propanal, and carnosine-propanol were significantly associated with males ( < 0.02) and those of Caucasian ethnicity ( < 0.02). Levels of carnosine-propanol were significantly higher in never-smokers ( = 0.001) but lower in current smokers ( = 0.037). This conjugate also demonstrated a negative association with mean-daily particulate air pollution (PM) levels ( = 0.01).
CONCLUSIONS
These findings suggest that urinary levels of carnosine-propanol may inform as to risk from inhaled pollutants.
Topics: 1-Propanol; Adult; Air Pollutants; Aldehydes; Biological Monitoring; Carnosine; Female; Humans; Inhalation Exposure; Male; Middle Aged; Smoking
PubMed: 33179563
DOI: 10.1080/08958378.2020.1845257 -
Forensic Science International Dec 2022The determination of various volatiles in postmortem blood samples has been reported in many previous studies. The presence of some of them in postmortem specimens...
The determination of various volatiles in postmortem blood samples has been reported in many previous studies. The presence of some of them in postmortem specimens reflects microbial activity in the sample while others are detected mainly after consumption of alcoholic beverages or due to antemortem metabolic processes. This contribution aims to determine in 1954 postmortem blood samples, from respective number of unnatural deaths autopsy cases, the frequency of detection of some common volatile compounds, including acetaldehyde, acetone, 2-propanol, ethyl acetate, methanol, as well as, the higher alcohols 1-propanol, 1-butanol, isobutanol and 2-methyl-1-butanol and 3-methyl-1-butanol; moreover, their patterns in respect to the ethanol and 1-propanol concentrations and the putrefaction state of the corpse at autopsy. Acetone was the most frequently detected volatile (82 %), followed by acetaldehyde (44 %) and 2-propanol (34 %). Methanol was detected in 12 % of the samples and only in the presence of ethanol. The most frequently detected higher alcohol was 1-propanol (51 %), followed by isobutanol (8.5 %), 1-butanol (3.6 %) and methyl-butanols (2.0%); the latter three higher alcohols were detected in the presence of 1-propanol indicating possibly a common origin. Samples from cases with putrefaction had higher 1-propanol concentrations, than those without putrefaction, and, moreover, they were significantly correlated with 1-butanol concentrations.
Topics: Humans; Ethanol; 1-Propanol; 1-Butanol; Acetone; Methanol; Autopsy; Molecular Weight; 2-Propanol; Acetaldehyde; Postmortem Changes
PubMed: 36283278
DOI: 10.1016/j.forsciint.2022.111503 -
Ecotoxicology and Environmental Safety Dec 2023Chronic toxicity tests on adult and larval honey bees (Apis mellifera) can require the use of dietary additives (solvents, emulsifiers, adjuvants and viscosifier agents)...
Chronic toxicity tests on adult and larval honey bees (Apis mellifera) can require the use of dietary additives (solvents, emulsifiers, adjuvants and viscosifier agents) when the active ingredient of plant protection products cannot be dissolved or does not remain stable and homogeneous within the test diets. Acetone is the widely used and accepted solvent allowed within the international regulatory guidelines, but it can be ineffective in keeping certain compounds in solution and can cause toxicity to adults and larvae. In this publication, we present an evaluation of alternative additives in adult and larval diets. Six dietary additives including five solvents (ethanol, isopropanol, n-propanol, propylene glycol and triethylene glycol) and a viscosifier agent (xanthan gum) at five concentrations along with a negative control and a solvent control (acetone) were investigated at seven laboratories. The safe levels for bees were determined for each of the additives used in the 10-day chronic adult and 22-day chronic larval tests. In the 10-day chronic adult study, ethanol and isopropanol were found to be safe at concentrations ≤ 5.0 %, while xanthan gum can be reliably used at concentrations ≤ 0.1 %. Greater variability across laboratories was observed for N-propanol, propylene glycol, and triethylene glycol and these agents may cause mortality when added to diets at concentrations above 0.25-0.5 %. The safe levels of additives to larval diet in the 22-day chronic larval test had a greater variability and were generally lower than what were observed for adult diet. Our results do not recommend the inclusion of ethanol or n-propanol into the larval diet, and isopropanol, propylene glycol, and triethylene glycol may cause mortality at concentrations above 0.25-0.5 %. Safe levels for xanthan gum were more variable than what was observed for adults, but it can be used reliably at concentrations ≤ 0.05 %. Our analyses conclude that several additives can be integrated successfully in honey bee laboratory bioassays at levels that cause low mortality to adults and larvae.
Topics: Bees; Animals; Larva; Acetone; 2-Propanol; 1-Propanol; Laboratories; Diet; Solvents; Ethanol; Propylene Glycols
PubMed: 38000305
DOI: 10.1016/j.ecoenv.2023.115718 -
Preparative Biochemistry & Biotechnology 2019A propanol-tolerant neutral protease was purified and characterized from sp. ZG20 in this study. This protease was purified to homogeneity with a specific activity of...
A propanol-tolerant neutral protease was purified and characterized from sp. ZG20 in this study. This protease was purified to homogeneity with a specific activity of 26,655 U/mg. The recovery rate and purification fold of the protease were 13.7% and 31.5, respectively. The SDS-PAGE results showed that the molecular weight of the protease was about 29 kDa. The optimal temperature and pH of the protease were 45 °C and 7.0, respectively. The protease exhibited a good thermal- and pH stability, and was tolerant to 50% propanol. Mg, Zn, K, Na and Tween-80 could improve its activity. The calculated and values of the protease towards α-casein were 12.74 mg/mL and 28.57 µg/(min mL), respectively. This study lays a good foundation for the future use of the neutral protease from sp. ZG20.
Topics: 1-Propanol; Bacillus; Detergents; Electrophoresis, Polyacrylamide Gel; Enzyme Stability; Hydrogen Peroxide; Hydrogen-Ion Concentration; Ions; Metals; Peptide Hydrolases; Solvents; Substrate Specificity; Surface-Active Agents; Temperature
PubMed: 31050583
DOI: 10.1080/10826068.2019.1605526 -
Langmuir : the ACS Journal of Surfaces... Sep 2022The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The...
The DNA origami technique allows the precise synthesis of complex, biocompatible nanomaterials containing small molecules, biomolecules, and inorganic nanoparticles. The negatively charged phosphates in the backbone make DNA highly water-soluble and require salts to shield its electrostatic repulsion. DNA origamis are therefore not soluble in most organic solvents. While this is not problematic for applications in biochemistry, biophysics, or nanomedicine, other potential applications, processes, and substrates are incompatible with saline solutions, which include the synthesis of many nanomaterials, and reactions in templated synthesis, the operation of nanoelectronic devices, or semiconductor fabrication. To overcome this limitation, we coated DNA origami with amphiphilic poly(ethylene glycol) polylysine block copolymers and transferred them into various organic solvents including chloroform, dichloromethane, acetone, or 1-propanol. Our approach maintains the shape of the nanostructures and protects functional elements bound to the structure, such as fluorophores, gold nanoparticles, or proteins. The DNA origami polyplex micellization (DOPM) strategy hence enables solubilization or a phase transfer of complex structures into various organic solvents, which significantly expands the use of DNA origami for a range of potential applications and technical processes.
Topics: 1-Propanol; Acetone; Chloroform; DNA; Gold; Metal Nanoparticles; Methylene Chloride; Nanostructures; Phosphates; Polyethylene Glycols; Polylysine; Polymers; Salts; Solubility; Solvents; Water
PubMed: 36103620
DOI: 10.1021/acs.langmuir.2c01508 -
Journal of Applied Toxicology : JAT Mar 20242-Amino-2-methyl-1-propanol (AMP™) is a widely used pH stabilizer in personal care products (PCPs); thus, the safety implications of dermal AMP exposure remain of... (Review)
Review
2-Amino-2-methyl-1-propanol (AMP™) is a widely used pH stabilizer in personal care products (PCPs); thus, the safety implications of dermal AMP exposure remain of interest. We have previously reported that exposure to AMP in PCPs when used as intended is not anticipated to result in an increased risk of hepatotoxicity (primarily steatosis and altered phospholipid homeostasis). The current study focuses on AMP in PCP's potential for developmental and reproductive toxicity (DART) in humans, based on data from animal studies. Animal studies suggest that exposure to AMP can result in post-implantation loss. However, such effects occur at maternally toxic doses, posing a challenge for determining appropriate hazard classifications in the context of relevant consumer use scenarios. Our assessment concluded that human exposure to AMP in PCPs is not anticipated to result in DART at non-maternally toxic doses. Further, mode of action (MOA) analysis elucidated the potential biological pathways underlying DART effects observed in high-dose animal studies, such that perturbation of uterine choline synthesis was the most well-supported MOA hypothesis. Downstream uterine effects might reflect choline-dependent changes in epigenetic control of pathways important for implantation maintenance and uterine cell energetics. Since AMP-induced post-implantation loss occurs at doses higher than pathology related to liver toxicity, maintaining AMP exposures from exceeding the onset dose for maternal liver effects will also be protective of DART effects. Furthermore, dermal exposure to AMP expected from the use of PCPs is highly unlikely to result in toxicologically significant systemic AMP concentrations; thus, DART is not anticipated.
Topics: Animals; Humans; Reproduction; Propanolamines; Embryo Implantation; Choline
PubMed: 37715655
DOI: 10.1002/jat.4539 -
Journal of Agricultural and Food... Feb 2021The -propanol produced by has a remarkable effect on the taste and flavor of Chinese Baijiu. The -propanol metabolism-related genes were deleted to evaluate the role in...
The -propanol produced by has a remarkable effect on the taste and flavor of Chinese Baijiu. The -propanol metabolism-related genes were deleted to evaluate the role in the synthesis of -propanol to ascertain the key genes and pathways for the production of -propanol by . The results showed that 3, 1, 6, 1, 5, and 082 were the key genes affecting the -propanol metabolism in yeast. The -propanol concentrations of α5Δ1, α5Δ3, and α5Δ6 increased by 121.75, 22.75, and 17.78%, respectively, compared with α5. The -propanol content of α5Δ1, α5Δ5, and α5Δ082 decreased by 24.98, 8.35, and 8.44%, respectively, compared with α5. The contents of intermediate metabolites were measured, and results showed that the mutual transformation of glycine and threonine in the threonine pathway and the formation of propanal from 2-ketobutyrate were the core pathways for the formation of -propanol. Additionally, 082 played important role in the synthesis of -propanol by directly producing 2-ketobutyric acid through l-homoserine. This study provided valuable insights into the -propanol synthesis in and the theoretical basis for future optimization of yeast strains in Baijiu making.
Topics: 1-Propanol; Fermentation; Genes, Regulator; Metabolic Networks and Pathways; Saccharomyces cerevisiae; Saccharomyces cerevisiae Proteins; Wine
PubMed: 33502852
DOI: 10.1021/acs.jafc.0c06810 -
Molecules (Basel, Switzerland) Jun 2020The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of...
The impaired activity of tyrosinase and laccase can provoke serious concerns in the life cycles of mammals, insects and microorganisms. Investigation of inhibitors of these two enzymes may lead to the discovery of whitening agents, medicinal products, anti-browning substances and compounds for controlling harmful insects and bacteria. A small collection of novel reversible tyrosinase and laccase inhibitors with a phenylpropanoid and hydroxylated biphenyl core was prepared using naturally occurring compounds and their activity was measured by spectrophotometric and electrochemical assays. Biosensors based on tyrosinase and laccase enzymes were constructed and used to detect the type of protein-ligand interaction and half maximal inhibitory concentration (IC). Most of the inhibitors showed an IC in a range of 20-423 nM for tyrosinase and 23-2619 nM for laccase. Due to the safety concerns of conventional tyrosinase and laccase inhibitors, the viability of the new compounds was assayed on PC12 cells, four of which showed a viability of roughly 80% at 40 µM. In silico studies on the crystal structure of laccase enzyme identified a hydroxylated biphenyl bearing a prenylated chain as the lead structure, which activated strong and effective interactions at the active site of the enzyme. These data were confirmed by in vivo experiments performed on the insect model .
Topics: Animals; Catalytic Domain; Cell Survival; Crystallography, X-Ray; Enzyme Inhibitors; Hydroxylation; Laccase; Models, Molecular; Monophenol Monooxygenase; PC12 Cells; Phenol; Propanols; Protein Conformation; Rats; Tenebrio
PubMed: 32545293
DOI: 10.3390/molecules25112709 -
Molecular Diversity Oct 2022Eco-friendly, low-cost and high-yielding synthetic route toward imidazoles and oxazoles has been developed....
Eco-friendly, low-cost and high-yielding synthetic route toward imidazoles and oxazoles has been developed. 1-(4,6-Dimethylpyrimidin-2-yl)-2-(alkylamino)-1,5-dihydro-4H-imidazol-4-one 3a-c have been synthesized via regiospecific reaction of ethyl 2-(N-(4,6-dimethylpyrimidin-2-yl)cyanamide)acetate 1 with primary aliphatic amines in water as green solvent. While, the reaction between 4,6-dimethylpyrimidin-2-yl(2-oxo-2-phenylethyl)cyanamide 2 and primary aliphatic amines using water and/or iso-propanol as green solvents afforded 3-(4,6-dimethylpyrimidin-2-yl)-5-phenyl-1,3-oxazole-2(3H)-imine 6 and 1-(4,6-dimethylpyrimidin-2-yl)-N-alkyl-4-phenyl-1H-imidazol-2-amine 7a-d, respectively.
Topics: Amines; Cyanamide; Cyclization; Imidazoles; Oxazoles; Propanols; Solvents; Water
PubMed: 35220547
DOI: 10.1007/s11030-022-10401-z