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Biotechnology Progress Jul 2022Cell culture medium (CCM) formulations are chemically defined to reduce lot-to-lot variability and complexity of the medium while still providing all essential nutrients...
Cell culture medium (CCM) formulations are chemically defined to reduce lot-to-lot variability and complexity of the medium while still providing all essential nutrients supporting cell growth and productivity of various cell lines. However, raw material impurities may still introduce variations and inconsistencies to final CCM formulations. In one of our previous studies (Weiss et al. Biotechnol Prog. 2021;37(4):e3148), we have demonstrated the impact of iron raw material impurity on Chinese hamster ovary (CHO) cell performance and critical quality attributes (CQAs) of recombinant proteins within the Cellvento® 4CHO CCM platform by identifying manganese impurity as the main root cause for improved cell performance and altered glycosylation profiles. This study sought to investigate the impact of iron raw material impurities within another medium platform, namely EX-CELL® Advanced CHO Fed-Batch-Medium. As opposed to previously published results, in this platform, copper instead of manganese impurity present within the used ferric ammonium citrate (FAC) iron source was responsible for an improved cell performance of a CHOZN® cell line and a slight difference in CQAs of the produced recombinant protein. The use of tightly controlled raw material specifications or the use of low impurity iron sources is therefore crucial to minimize the impact of impurities on cell performance in any CCM platform and thereby guarantee consistent and reproducible cell culture processes.
Topics: Animals; CHO Cells; Cell Culture Techniques; Copper; Cricetinae; Cricetulus; Culture Media; Iron; Manganese; Recombinant Proteins
PubMed: 35318833
DOI: 10.1002/btpr.3251 -
Journal of Pharmaceutical and... Jan 2023The first, sensitive, and rapid chiral method was developed for enatioseperations and determination of cabotegravir and its enantiomeric impurities by using HPLC and...
Chiral LC method development: Stereo-selective separation, characterization, and determination of cabotegravir and related RS, RR, and SS isomeric impurities on coated cellulose-based chiral stationary phase by HILIC-LC and LC-MS.
The first, sensitive, and rapid chiral method was developed for enatioseperations and determination of cabotegravir and its enantiomeric impurities by using HPLC and LC-MS. Cabotegravir is an antiretroviral medication used for the treatment of HIV/AIDS approved by the food and drugs administration (FDA) in the year 2021. The cabotegravir chiral separation was achieved on the coated cellulose-tris (4-chloro-3-methyl phenyl carbamate) (CHIRALCEL OX-3R) column in HILIC mode and the total run time is less than 15 min. The effects of mobile phase composition, elution mode, and percentage of organic modifier as well as the effect of mobile phase-additives and column temperature were investigated on selectivity, resolution, and peak symmetry. The mobile phase consisted of acetonitrile and water with 0.1% (v/v) addition of formic acid additive with the flow rate of 1 mLmin. UV detection was carried out at 220 nm. The calibration curves of cabotegravir and its enantiomers were linear over the concentration range of 0.04-1.125 µgmL. The limits of detection and quantification for cabotegravir and its enantiomer (RS isomer) were ≤ 0.02 and ≤ 0.06, and the RR and SS-isomers limits were ≤ 0.02 and 0.03 µgmL respectively. It was demonstrated that the proposed method is selective, precise, and robust. Finally, the validated method was applied for the determination and identification of cabotegravir and its chiral enantiomers in the bulk drugs by using HPLC and LC-MS techniques.
Topics: Chromatography, Liquid; Cellulose; Tandem Mass Spectrometry; Stereoisomerism; Chromatography, High Pressure Liquid; Pharmaceutical Preparations
PubMed: 36194910
DOI: 10.1016/j.jpba.2022.115062 -
ChemSusChem Aug 2022Periodate, a platform oxidizer, can be electrochemically recycled in a self-cleaning process. Electrosynthesis of periodate is well established at boron-doped diamond...
Periodate, a platform oxidizer, can be electrochemically recycled in a self-cleaning process. Electrosynthesis of periodate is well established at boron-doped diamond (BDD) anodes. However, recovered iodate and other iodo species for recycling can contain traces of organic impurities from previous applications. For the first time, it was shown that the organic impurities do not hamper the electrochemical re-oxidation of used periodate. In a hydroxyl-mediated environment, the organic compounds form CO and H O during the degradation process. This process is often referred to as "cold combustion" and provides orthogonal conditions to periodate synthesis. To demonstrate the strategy, different dyes, pharmaceutically active ingredients, and iodine compounds were added as model contaminations into the process of electrochemical periodate production. UV/Vis spectroscopy, NMR spectroscopy, and mass spectrometry (MS) were used to monitor the degradation of organic molecules, and liquid chromatography-MS was used to control the purity of periodate. As a representative example, dimethyl 5-iodoisophthalate (2 mm), was degraded in 90, 95, and 99 % while generating 0.042, 0.054, and 0.082 kilo equiv. of periodate, respectively. In addition, various organic iodo compounds could be fed into the periodate generation for upcycling such iodo-containing waste, for example, contrast media.
Topics: Boron; Diamond; Electrodes; Organic Chemicals; Oxidation-Reduction; Periodic Acid; Water Pollutants, Chemical
PubMed: 35670517
DOI: 10.1002/cssc.202200874 -
Nanoscale Research Letters Feb 2020The effect of unintentionally doped hydrogen on the properties of Mg-doped p-GaN samples grown via metal-organic chemical vapor deposition (MOCVD) is investigated...
The effect of unintentionally doped hydrogen on the properties of Mg-doped p-GaN samples grown via metal-organic chemical vapor deposition (MOCVD) is investigated through room temperature photoluminescence (PL) and Hall and secondary ion mass spectroscopy (SIMS) measurements. It is found that there is an interaction between the residual hydrogen and carbon impurities. An increase of the carbon doping concentration can increase resistivity of the p-GaN and weaken blue luminescence (BL) band intensity. However, when hydrogen incorporation increased with carbon doping concentration, the increase of resistivity caused by carbon impurity is weaken and the BL band intensity is enhanced. This suggests that the co-doped hydrogen not only passivate Mg, but also can passivate carbon impurities in Mg-doped p-GaN.
PubMed: 32040646
DOI: 10.1186/s11671-020-3263-9 -
Advanced Materials (Deerfield Beach,... Nov 2020Metal-organic frameworks (MOFs) have emerged as an important and unique class of functional crystalline hybrid porous materials in the past two decades. Due to their... (Review)
Review
Metal-organic frameworks (MOFs) have emerged as an important and unique class of functional crystalline hybrid porous materials in the past two decades. Due to their modular structures and adjustable pore system, such distinctive materials have exhibited remarkable prospects in key applications pertaining to adsorption such as gas storage, gas and liquid separations, and trace impurity removal. Evidently, gaining a better understanding of the structure-property relationship offers great potential for the enhancement of a given associated MOF property either by structural adjustments via isoreticular chemistry or by the design and construction of new MOF structures via the practice of reticular chemistry. Correspondingly, the application of isoreticular chemistry paves the way for the microfine design and structure regulation of presented MOFs. Explicitly, the microfine tuning is mainly based on known MOF platforms, focusing on the modification and/or functionalization of a precise part of the MOF structure or pore system, thus providing an effective approach to produce richer pore systems with enhanced performances from a limited number of MOF platforms. Here, the latest progress in this field is highlighted by emphasizing the differences and connections between various methods. Finally, the challenges together with prospects are also discussed.
PubMed: 32671894
DOI: 10.1002/adma.202002563 -
Water Research Jan 2021Chlorine dioxide (ClO) is a prevalently used disinfectant alternative to chlorine, due to its effectiveness in pathogen inactivation and low yields of organic...
Chlorine dioxide (ClO) is a prevalently used disinfectant alternative to chlorine, due to its effectiveness in pathogen inactivation and low yields of organic halogenated disinfection byproducts (DBPs). However, during ClO generation, chlorine is inevitably introduced into the obtained ClO solution as an "impurity", which could compromise the merits of ClO disinfection. In this study, drinking water disinfection with ClO containing 0‒25% chlorine impurity (i.e., at Cl to ClO mass ratios of 0‒25%) was simulated, and the effect of chlorine impurity on the DBP formation and developmental toxicity of the finished water was evaluated. With increasing the chlorine impurity in ClO, the chlorite level kept decreasing and the chlorate level gradually increased; meanwhile, an unexpected trend from decline to rise was observed for the total organic halogenated DBPs, with the minimum level appearing at 5% chlorine impurity. To unravel the mechanisms for the variations of organic halogenated DBPs with chlorine impurity, a quantitative kinetic model was developed to simulate the formation of chlorinated, brominated, and iodinated DBPs in the ClO-disinfected drinking water. The modeling results indicated that reactions involving iodide accounted for the decrease of organic halogenated DBPs at a relatively low chlorine impurity level. In accordance with DBP formation, ClO with 5% chlorine impurity generated less toxic drinking water than pure ClO, while significantly higher developmental toxicity was induced until the chlorine impurity reached 25%. For E. coli inactivation, the presence of chlorine impurity enhanced the disinfection efficiency due to a synergistic effect of ClO and chlorine. Therefore, disinfection practices with ClO containing low chlorine impurity (e.g., <10%) might be favored (i.e., there is no need to eliminate low chlorine impurity in the ClO solution), while those containing high chlorine impurity should be concerned.
Topics: Chlorine; Chlorine Compounds; Disinfectants; Disinfection; Escherichia coli; Halogenation; Oxides; Water Pollutants, Chemical; Water Purification
PubMed: 33091806
DOI: 10.1016/j.watres.2020.116520 -
Environmental Science & Technology May 2020During the prebiotic era, radiolytic transformations in the oceans played a key role in purifying water from toxic impurities and, thus, played a role in the formation...
During the prebiotic era, radiolytic transformations in the oceans played a key role in purifying water from toxic impurities and, thus, played a role in the formation of the aquatic environment of our planet, making it suitable for the emergence of life. Today, the planet again faces the challenge of how to provide people with clean water. Therefore, it is reasonable to look back at past historical stages and again consider the possibility of neutralizing pollutants in water by means of radiolysis, which has already been tested by time. Modern radiolytic treatments can be much faster and safer thanks to the advent of powerful electron accelerators and high-rate electron beam treatment (ELT) of water and wastewater. Radiolytic treatment of water using accelerated electrons corresponds to the essence of advanced oxidative technologies and green chemistry. The ELT of water instantly generates a high concentration of short-lived radicals that can quickly neutralize and decompose chemical and bacterial pollutants. Due to the ability of accelerated electrons to penetrate into a substance, ELT provides the decomposition of both dissolved and suspended pollutants. The cleaning effect of ELT is due to the ability to inactivate toxic and chromophore functional groups, transform impurities into an easily removable form, damage the DNA of microorganisms and their spore forms, and increase the biodegradability of organic impurities. The use of ELT in water treatment provides significant savings in chemical reagents, thereby improving quality and reducing the number of cleaning steps. The compactness, high degree of automation of the equipment used, energy efficiency, high productivity, and excellent compatibility with traditional water treatment methods are important advantages of ELT. Unlike conventional chemicals, the excess radicals generated in the ELT process are converted back to water and hydrogen; thus, the chemical and corrosive activity of water does not increase. Equipping research institutes with electron accelerators, developing cheaper accelerators, and granting government support for pilot projects are key conditions for introducing ELT into water treatment practice.
Topics: Electrons; Wastewater; Water; Water Pollutants, Chemical; Water Purification
PubMed: 32267147
DOI: 10.1021/acs.est.0c00545 -
Journal of Pharmaceutical and... Feb 2023Bupivacaine was found to be unstable during the accelerated storage condition(40 ℃ and 75% relative humidity), and two degradation impurities with the same protonated...
Bupivacaine was found to be unstable during the accelerated storage condition(40 ℃ and 75% relative humidity), and two degradation impurities with the same protonated molecular ion were observed by high performance liquid chromatography-mass spectrometry (LC-MS). A semipreparative method was used to separate and purify the two impurities, and their structures were elucidated via comprehensive HR-MSMS and NMR spectroscopy analyses. Their stereo structures were characterized through single crystal X-ray diffraction. Meanwhile, an LC-MS method was developed and validated to quantify the two degradation impurities of bupivacaine. Chromatographic separation was performed on a C18 reversed-phase column (4.6 × 150 mm, 5 µm) using an equivalent elution with water and methanol. The limits of quantitation for the two degradation impurities (named RS1 and RS2) were 0.89 and 0.65 ng, respectively, and the average recoveries were in the range of 90∼108% and relative standard deviations were less than 5.0%. The proposed LC-MS method can be used to control the quality of bupivacaine and its formulations. DATA AVAILABILITY: Data will be made available on request.
Topics: Bupivacaine; Chromatography, Liquid; Chromatography, High Pressure Liquid; Mass Spectrometry; Methanol; Drug Contamination
PubMed: 36621282
DOI: 10.1016/j.jpba.2023.115236 -
Journal of Pharmaceutical and... May 2021Unknown chromatographic peaks, potential impurities, were observed in a series of related compounds. This led to the identification and characterization of tautomeric...
Unknown chromatographic peaks, potential impurities, were observed in a series of related compounds. This led to the identification and characterization of tautomeric equilibria. Structural elucidation was required to understand the potential impurity profile, thus impacting method development for quality control. In this work, characterization of the chemical structures, AZ13581258 and AZD5718, and equilibria of the tautomeric forms was performed using a range of advanced analytical techniques such as preparative chromatography, nuclear magnetic resonance (NMR), chromatographic detection by mass spectrometry (MS), MSMS, and ultraviolet spectroscopy (UV). Predictions using density functional theory (DFT) further explains and confirms the tautomer equilibria through predictions of reaction barrier energies, UV-spectra and NMR data. These investigations led to fully understand the impurity profile and to the development of a quality control method for AZD5718 drug substance and drug product. In conclusion, ring-chain tautomeric structures are predominately formed under acidic conditions, and the additional peaks observed in LC during organic impurity determination were found to originate from ring-chain closed tautomers in equilibria with the parent open form compound. Hence, the closed and open tautomer forms should all be considered as the same compound.
Topics: Drug Contamination; Isomerism; Mass Spectrometry; Pharmaceutical Preparations; Quality Control
PubMed: 33740606
DOI: 10.1016/j.jpba.2021.114020 -
Journal of Pharmaceutical and... Feb 2021A rapid, sensitive, and accurate high-performance liquid chromatography (HPLC) method was developed and validated for the separation and analysis of organic impurities...
A rapid, sensitive, and accurate high-performance liquid chromatography (HPLC) method was developed and validated for the separation and analysis of organic impurities in erythromycin stearate tablets. The method separates Erythromycin, Erythromycin B, Erythromycin C and nine impurities (EP Impurity A, B, C, D, E, F, H, I and M). The chromatographic separation was achieved on a Waters XBridge C18 (100 mm × 4.6 mm, 3.5 μm) column. The mobile phase comprised of 0.4 % ammonium hydroxide in water and methanol delivered in a gradient mode. The compounds of interest were monitored at 215 nm. The stability-indicating capability of this method was evaluated by performing stress studies. Erythromycin was found to degrade significantly under acid, base, and oxidative stress conditions and it was only stable under thermal and photolytic degradation conditions. The degradation products were well resolved from the erythromycin peaks. In addition, the major degradants formed under stress conditions were characterized by ultra-high-performance liquid chromatography coupled with Single-Quadrupole Mass Spectrometer (UHPLC-QDa). The method was validated to fulfill International Conference on Harmonization (ICH) requirements and this validation included specificity, linearity, limit of detection (LOD), limit of quantification (LOQ), accuracy, precision, and robustness. The developed method could be incorporated into the USP monograph and applied for routine quality control analysis of erythromycin stearate tablets.
Topics: Chromatography, High Pressure Liquid; Drug Stability; Erythromycin; Reproducibility of Results; Tablets
PubMed: 33388642
DOI: 10.1016/j.jpba.2020.113858