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Molecules (Basel, Switzerland) Apr 2020The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. -Aminophenol (PAP) is one of the main impurities of paracetamol...
The presence of impurities can drastically affect the efficacy and safety of pharmaceutical entities. -Aminophenol (PAP) is one of the main impurities of paracetamol (PA) that can potentially show toxic effects such as maternal toxicity and nephrotoxicity. The removal of PAP from PA is challenging and difficult to achieve through regular crystallization approaches. In this regard, we report four new salts of PAP with salicylic acid (SA), oxalic acid (OX), l-tartaric acid (TA), and (1)-(+)-10-camphorsulfonic acid (CSA). All the PAP salts were analyzed using single-crystal X-ray diffraction, powder X-ray diffraction, infrared spectroscopy, differential scanning calorimetry, and thermogravimetric analysis. The presence of minute amounts of PAP in paracetamol solids gives a dark color to the product that was difficult to remove through crystallization. In our study, we found that the addition of small quantities of the aforementioned acids helps to remove PAP from PA during the filtration and washings. This shows that salt formation could be used to efficiently remove challenging impurities.
Topics: Aminophenols; Crystallography, X-Ray; Drug Contamination; Models, Molecular; Molecular Structure; Organic Chemicals; Pharmaceutical Preparations; Powders; Salts
PubMed: 32326160
DOI: 10.3390/molecules25081910 -
RSC Advances Mar 2019With an increase in the organic acid requirement, the production of organic acids has been increased over the years. To achieve cost-effective production of organic... (Review)
Review
With an increase in the organic acid requirement, the production of organic acids has been increased over the years. To achieve cost-effective production of organic acids, efficient recovery processes are needed. Electro-membrane processes, including electrodialysis (ED), electrometathesis (EMT), electro-ion substitution (EIS), electro-electrodialysis (EED), electrodialysis with bipolar membrane (EDBM), and electrodeionization (EDI), are promising technologies for the recovery of organic acids. In the electro-membrane processes, organic acids are separated from water and other impurities based on the electro-migration of ions through ion-exchange membranes. These processes can recover various types of organic acids from the fermentation broth with high recovery yield and low energy consumption. In addition, the integration of fermentation and the electro-membrane process can improve the acid recovery with lower byproduct concentration and energy consumption.
PubMed: 35521162
DOI: 10.1039/c8ra09227c -
Forensic Science International Mar 20174-Methoxymethamphetamine (PMMA) was synthesised from star anise and from 4-methoxytoluene and the organic impurity profiles examined. These two starting materials are...
4-Methoxymethamphetamine (PMMA) was synthesised from star anise and from 4-methoxytoluene and the organic impurity profiles examined. These two starting materials are unrestricted chemicals in many jurisdictions and contain the requisite functional groups and are thus well suited for clandestine manufacturers. trans-Anethole was extracted from star anise and oxidised to 4-methoxyphenyl-2-propanone (PMP2P). 4-Methoxytoluene was oxidised to anisaldehyde, converted to 4-methoxyphenyl-2-nitropropene, and then reduced to PMP2P. The PMP2P obtained by both methods was then converted to PMMA via the Leuckart reaction. 4-Methoxymethamphetamine hydrochloride (PMMA·HCl) was synthesised from PMMA using hydrogen chloride gas. Both of the examined synthetic methods were found to be feasible routes into PMMA·HCl. The products of each step were analysed by gas chromatography-mass spectrometry (GC-MS) and proton nuclear magnetic resonance spectroscopy (H NMR). Impurities were examined in an attempt to identify route specific compounds, which may provide valuable information about the synthetic pathway and precursors.
PubMed: 28065556
DOI: 10.1016/j.forsciint.2016.11.041 -
Advanced Materials (Deerfield Beach,... Jan 2019Controlling the pn-type behavior of a semiconductor such as silicon by adding an extremely small quantity of an impurity (doping) is a central part of inorganic... (Review)
Review
Controlling the pn-type behavior of a semiconductor such as silicon by adding an extremely small quantity of an impurity (doping) is a central part of inorganic semiconductor electronics since the 20th century. Recent progress in the doping of organic semiconductors strongly suggests the advent of a new era of doped organic semiconductors. Here, the principles and effects of doping at the level of parts per million (ppm) in organic semiconductor films and single crystals are described, including descriptions of complete pn-control, doping sensitization, ppm doping using an extremely low-speed deposition technique reaching 10 nm s , and emerging ppm-level doping effects, such as trap filling, majority carriers, homojunction formation, and decreased mobility, as well as ppm-level doping effects in organic single crystals measured by the Hall effect, which shows a doping efficiency of 24%. The Wannier excitonic doping of organic single crystals possessing band conduction and the defect science of organic single crystals related to carrier trapping and scattering are introduced as a new scientific field. The dawn of organic single-crystal electronics is also discussed.
PubMed: 30118548
DOI: 10.1002/adma.201801236 -
Separation Science Plus Jan 2020Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug...
Many over-the-counter drug products lack official compendial analytical methods. As a result, the United States Pharmacopeia and the United States Food and Drug Administration are seeking to develop and validate new methods to establish analysis standards for the assessment of the pharmaceutical quality of over-the-counter drug products. Diphenhydramine and phenylephrine hydrochloride oral solution, a combination drug product, was identified as needing a compendial standard. Therefore, an ultra-high-performance liquid chromatography method was developed to separate and quantify the two drug compounds and eleven related organic impurities. As part of a robustness study, the separation was demonstrated using different high-performance liquid chromatography systems and columns from different manufacturers, and showed little dependence with changes in flow rate, column temperature, detection wavelength, injection volume and mobile phase gradient. The method was then validated conformant with the International Council for Harmonisation guidelines. For impurities, adequate specificity, linearity, accuracy and precision were demonstrated. For assay, a slight modification to the injection volume was necessary to achieve adequate analytical performance. With successful development and validation, these methods were shown to be suitable for their intended purpose and may be considered for adoption as compendial procedures.
PubMed: 32076656
DOI: 10.1002/sscp.201900084 -
Forensic Science International Apr 2020This work examines organic impurity profiles of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from the "pre-precursors" catechol...
This work examines organic impurity profiles of 3,4-methylenedioxymethamphetamine (MDMA) that has been synthesised from the "pre-precursors" catechol (1,2-dihydroxybenzene) and eugenol, via a safrole intermediate. MDMA was synthesised from the catechol- and eugenol-derived safrole intermediate via two routes, which resulted in the synthesis of MDMA from catechol via two routes (Route 1A and 1B) and from eugenol via two routes (Route 2A and 2B). Twelve organic impurities were identified in MDMA synthesised via Routes 1A and 1B, and eleven organic impurities were identified in MDMA synthesised via Routes 2A and 2B. Route specific organic impurities were identified in MDMA that indicated the "pre-precursors" catechol and eugenol were used in the respective synthetic routes. Route specific organic impurities were also identified in MDMA that indicated the route used to synthesise safrole from the "pre-precursor" and the route used to synthesise MDMA from safrole. Thus, the use of the "pre-precursors" catechol and eugenol and the synthetic route utilised could be ascertained by the organic impurity profiling of MDMA under the conditions used here.
PubMed: 32070849
DOI: 10.1016/j.forsciint.2020.110176 -
Journal of AOAC International Sep 2018Though synthetic organic colorants are used in various applications nowadays, there is the concern that impurities by-produced during the manufacturing and degradation... (Review)
Review
Though synthetic organic colorants are used in various applications nowadays, there is the concern that impurities by-produced during the manufacturing and degradation products in some of these colorants are persistent organic pollutants and carcinogens. Thus, it is important to identify the synthetic organic colorants in various products, such as commercial paints, ink, cosmetics, food, textile, and plastics. Dyes, which are soluble in water and other solvents, could be analyzed by chromatographic methods. In contrast, it is difficult to analyze synthetic organic pigments by these methods because of their insolubility. This review is an overview of mass spectrometric analysis of synthetic organic pigments by various ionization methods. We highlight a recent study of textile samples by atmospheric pressure solid analysis probe MS. Furthermore, the mass spectral features of synthetic organic pigments and their separation from other components such as paint media and plasticizers are discussed.
Topics: Coloring Agents; Cosmetics; Food Analysis; Mass Spectrometry; Organic Chemicals; Paint; Textiles
PubMed: 29669623
DOI: 10.5740/jaoacint.18-0049 -
Biomedical Chromatography : BMC Feb 2023Apalutamide, an androgen receptor inhibitor, is used to treat prostate cancer. A stability-indicating high-performance liquid chromatography method was developed for the...
Apalutamide, an androgen receptor inhibitor, is used to treat prostate cancer. A stability-indicating high-performance liquid chromatography method was developed for the estimation of assay and organic impurities of apalutamide in drug substance and in tablet dosages using Design of Experiments. The chromatographic separation was achieved within 30 min using Atlantis dC , 100 × 4.6 mm, 3.0 μm and the binary gradient program (10 mm KH PO , pH 3.5; acetonitrile). The detection wavelength, flow rate, column temperature and injection volume used were 270 nm, 1.0 ml/min, 45°C and 10 μl, respectively. The interaction of independent variables (pH, column temperature and flow rate) and their influences on HPLC parameters were studied using a central composite design, and then the peak separation and elution behaviors between apalutamide and its seven impurities were determined. The method validation was performed for linearity, detection limit, quantitation limit, accuracy, precision and robustness as per the International Conference on Harmonization. A high-quality recovery with good precision (91.7-106.0%) and correlations (r > 0.997) within a linear range of 0.12-2.24 μg/ml (0.05-0.3%, w/w) were achieved consistently for assay and organic impurities of apalutamide. The stability-indicating characteristics of the proposed method were assessed through forced degradation and mass balance studies. An effort was made to figure out the chemical structures of newly formed degradation products (DP1-DP5) using LC-MS/MS.
Topics: Male; Humans; Chromatography, Liquid; Chromatography, High Pressure Liquid; Tandem Mass Spectrometry; Antineoplastic Agents; Drug Contamination; Drug Stability; Reproducibility of Results
PubMed: 36409057
DOI: 10.1002/bmc.5549 -
Drug Testing and Analysis Mar 2017This work examined the synthesis and organic impurity profile of methylone prepared from catechol. The primary aim of this work was to determine whether the synthetic...
This work examined the synthesis and organic impurity profile of methylone prepared from catechol. The primary aim of this work was to determine whether the synthetic pathway used to prepare 3,4-methylenedioxypropiophenone could be ascertained through analysis of the synthesized methylone. The secondary aim was the structural elucidation and origin determination of the organic impurities detected in methylone and the intermediate compounds. The organic impurities present in the reaction products were identified using GC-MS and NMR spectroscopy. Six organic impurities were detected in 1,3-benzodioxole and identified as the 1,3-benzodioxole dimer, 1,3-benzodioxole trimer, [1,3] dioxolo[4,5-b]oxanthrene, 4,4'-, 4,5'-, and 5,5'-methylenebis-1,3-benzodioxole. Six organic impurities were detected in 3,4-methylenedioxypropiophenone and identified as (2-hydroxyphenyl) propanoate, [2-(chloromethoxy) phenyl] propanoate, (2-propanoyloxyphenyl)propanoate, 5-[1-(1,3-benzodioxol-5-yl)prop-1-enyl]-1,3-benzodioxole, (5E)- and (5Z)-7-(1,3-benzodioxol-5-yl)-5-ethylidene-6-methyl-cyclopenta[f][1,3]benzodioxole). Exploratory synthetic experiments were also conducted to unambiguously identify the organic impurities detected in 3,4-methylenedioxypropiophenone. Two organic impurities were detected in 5-bromo-3,4-methylenedioxypropiophenone and identified as [2-(chloromethoxy)phenyl] propanoate and 3,4-methylenedioxypropiophenone. Five organic impurities were detected in methylone and identified as 3,4-methylenedioxypropiophenone, 1-(1,3-benzodioxol-5-yl)-N-methyl-propan-1-imine, 1-(1,3-benzodioxol-5-yl)-2-methylimino-propan-1-one, 1-(1,3-benzodioxol-5-yl)-N1,N2-dimethyl-propane-1,2-diimine and butylated hydroxytoluene. The origin of these organic impurities was also ascertained, providing valuable insight into the chemical profiles of methylone and the intermediate compounds. However, neither the catechol precursor nor the 1,3-benzodioxole intermediate could be identified based on the organic impurities detected in the synthesized methylone using standard techniques. This demonstrated that the organic impurity profiling of methylone had limitations in the determination of precursor chemical and synthetic pathways used. Copyright © 2017 John Wiley & Sons, Ltd.
Topics: Catechols; Central Nervous System Stimulants; Dimerization; Dioxoles; Drug Contamination; Gas Chromatography-Mass Spectrometry; Magnetic Resonance Spectroscopy; Methamphetamine
PubMed: 27886663
DOI: 10.1002/dta.2140 -
Proceedings of the National Academy of... Apr 2022Knowledge of deformation mechanisms in aragonite, one of the three crystalline polymorphs of CaCO3, is essential to understand the overall excellent mechanical...
Knowledge of deformation mechanisms in aragonite, one of the three crystalline polymorphs of CaCO3, is essential to understand the overall excellent mechanical performance of nacres. Dislocation slip and deformation twinning were claimed previously as plasticity carriers in aragonite, but crystallographic features of dislocations and twins have been poorly understood. Here, utilizing various transmission electron microscopy techniques, we reveal the atomic structures of twins, partial dislocations, and associated stacking faults. Combining a topological model and density functional theory calculations, we identify complete twin elements, characters of twinning disconnection, and the corresponding twin shear angle (∼8.8°) and rationalize unique partial dislocations as well. Additionally, we reveal an unreported potential energy dissipation mode within aragonite, namely, the formation of nanograins via the pile-up of partial dislocations. Based on the microstructural comparisons of biogenic and abiotic aragonite, we find that the crystallographic features of twins are the same. However, the twin density is much lower in abiotic aragonite due to the vastly different crystallization conditions, which in turn are likely due to the absence of organics, high temperature and pressure differences, the variation in inorganic impurities, or a combination thereof. Our findings enrich the knowledge of intrinsic crystal defects that accommodate plastic deformation in aragonite and provide insights into designing bioengineering materials with better strength and toughness.
PubMed: 35357967
DOI: 10.1073/pnas.2122218119