Specific Impurities Research Articles

Impurities in Animal-Derived Medicines (Relevant Issues)

The global anthropogenic load on the biosphere results in a potentially unmanageable problem of ecosystem pollution with organic and inorganic impurities, which may carry significant risks for human health. Therefore, the development and production of medicinal products from raw materials of animal origin require a careful risk-based assessment of impurities that may be found in the finished product. The aim of the study was to categorise the impurities in animal-derived medicines, identify and characterise specific impurity groups, and suggest a control methodology. The article reviews the factors that allow grouping impurities in animal-derived medicines, namely, the origin (anthropogenic or natural), type (process- or raw material-related), nature (product-related or foreign), and presence (inherent or potential impurities). The authors note the necessity of considering the specific production conditions, the origin of raw materials, and the intended use of medicinal products to determine an optimal control strategy for each impurity group and to justify the level at which a specific impurity should be controlled (the raw material, active substance, or finished product). A product’s marketing authorisation application must contain comprehensive data on the choice of the control strategy for potential impurities, including a justification of the selected control level and the established limits, details of the chosen control procedures, and risk-assessment reports.

Spin-polarized imaging of the antiferromagnetic structure and field-tunable bound states in kagome magnet FeSn

Kagome metals are an exciting playground for the explorations of novel phenomena at the intersection of topology, electron correlations and magnetism. The family of FeSn-based kagome magnets in particular attracted a lot of attention for simplicity of the layered crystal structure and tunable topological electronic band structure. Despite a significant progress in understanding their bulk properties, surface electronic and magnetic structures are yet to be fully explored in many of these systems. In this work, we focus on a prototypical kagome metal FeSn. Using a combination of spin-averaged and spin-polarized scanning tunneling microscopy, we provide the first atomic-scale visualization of the layered antiferromagnetic structure at the surface of FeSn. In contrast to the field-tunable electronic structure of cousin material Fe3Sn2 that is a ferromagnet, we find that electronic density-of-states of FeSn is robust to the application of external magnetic field. Interestingly, despite the field insensitive electronic band structure, FeSn exhibits bound states tied to specific impurities with large effective moments that strongly couple to the magnetic field. Our experiments provide microscopic insights necessary for theoretical modeling of FeSn and serve as a spring board for spin-polarized measurements of topological magnets in general.

Anomalous Hall effect and ordinary Hall effect in variable range hopping regime of inhomogeneous ferromagnetic semiconductor

Anomalous Hall effect (AHE) and ordinary Hall effect (OHE) in variable range hopping regime of ferromagnetic semiconductor are important for understanding the localized impurity states at different energy levels within the band gap, and provides insight into the specific percolation networks of the thermally excited spin-polarized carriers. Here we report the experiments of both OHE and AHE in Mott and Efros variable range hopping regimes of inhomogeneous In0.27Co0.73O1-v ferromagnetic semiconductor films with the tunable localized electron density and localization length. We found an unusual scaling relation between the AHE coefficient RAH and the longitudinal resistivity ρxx, RAH∝ρxxβ with β>2 , which contrasts the scaling relation of OHE coefficient ROH∝ρxxα with α<1. More strikingly, the sign of AHE coefficient reverses with decreasing temperature for specific electron density. We argue that these surprising results are related to the specific impurity energy band structure of the oxygen vacancies within the band gap of inhomogeneous In0.27Co0.73O1-v ferromagnetic semiconductor films.

Growing Triticum aestivum Landraces in Rotation with Lupinus albus and Fallow Reduces Soil Depletion and Minimises the Use of Chemical Fertilisers

In north-western Spain, the cultivation of wheat landraces represents the pillar of quality Galician bread; today, a minimum of 25% Galician flour is required to produce bread under the auspices of the Protected Geographical Indication “Pan Galego”. The main objective of this study was to evaluate the effect of the rotation of two wheat landraces—‘Carral’ and ‘Caaveiro’—with lupin (sweet Lupinus albus), together with a fallow period, on crop yield and quality, as well as the environmental benefits of rotations over conventional monoculture systems. After the different agricultural activities, twelve agronomic parameters were analysed at the end of the third year. For the environmental analysis, the Life Cycle Assessment methodology was applied. The results showed a positive influence of rotation systems on wheat yield and quality parameters, reporting higher specific weight and lower impurities compared to monoculture. No significant differences were observed between wheat rotation and monoculture in other parameters related to baking quality, such as protein, wet gluten, baking strength (W), elasticity (L), tenacity (P), and swelling (G). However, soil quality influenced wheat quality independently of rotation, and higher organic matter and lower phosphorus produced higher W and P, respectively. Moreover, rotation had a positive effect on yield, up to 62% when fallow preceded wheat, and in reducing diseases, pests, and weeds. Finally, in terms of environmental performance, the best results were identified when lupin preceded wheat due to lower fertiliser application. In this regard, the worst profiles corresponded to the scenarios based on monoculture for both wheat landraces.

Citric ligand manipulated efficient spatially-separated reduction and immobilization of Cr(VI) upon electron-rich copper-iron oxides

In-situ removal of Cr(VI) by metallic (oxides) materials is generally limited by rapid loss of surface active sites, especially in neutral water/wastewater circumstances co-existing organic ligands impurity. This study has firstly demonstrated that synthesized magnetic electron-rich copper-iron oxides composites (Cu2O-Fe3O4) could successfully achieve amazingly efficient reductive immobilization of Cr(VI) induced by common citric ligand (Cit). As Cr(VI) reduced heterogeneously on the composites, immobilization of the generated Cr(III) was almost synchronous via a “spatially-separated” way and correlated linearly with simultaneous dissolved Cu. DFT calculations indicated more appropriate adsorption energy of Cit in realizing its preferential coordination on Fe3O4component surface and Cr(VI) adsorption on Cu2Ocomponent, as compared to oxalic, tartaric and EDTA ligands. The complexed Cit (Cit≡Fe3O4component) would promote internal electron transfer from Fe3O4component to Cu2Ocomponent then adsorbed Cr(VI), causing a highly improved electron efficiency of 72.25%. Most importantly, acting as a regulator of the continuously synchronous reduction and immobilization, Cit≡Fe3O4component would tendentiously chelate newborn Cu(II) at Cu2Ocomponent surface to release bulk Cu2+-Cit complexes, refreshing the reduction sites as well as favoring the Cr(III) immobilization of great stability at the exposed sites of Fe3O4component. This study has revealed that specific impurity ligands can stimulate and tune effective reductive immobilization of heavy metal oxyanions by electron-rich materials under near-neutral conditions, providing a new method towards the efficient treatment of Cr(VI) contaminated wastewaters.

Photochemical method for removing methane interference for improved gas analysis

Abstract. The development of laser spectroscopy has made it possible to measure minute changes in the concentrations of trace gases and their isotopic analogs. These single or even multiply substituted species occur at ratios from percent to below parts per million and contain important information concerning trace gas sources and transformations. Due to their low abundance, minimizing spectral interference from other gases in a mixture is essential. Options including traps and membranes are available to remove many specific impurities. Methods for removing CH4, however, are extremely limited as methane has low reactivity and adsorbs poorly to most materials. Here we demonstrate a novel method for CH4 removal via chlorine-initiated oxidation. Our motivation in developing the technique was to overcome methane interference in measurements of N2O isotopic analogs when using a cavity ring-down spectrometer. We describe the design and validation of a proof-of-concept device and a kinetic model to predict the dependence of the methane removal efficiency on the methane concentration [CH4], chlorine photolysis rate JCl2, chlorine concentration [Cl2] and residence time tR. The model was validated by comparison to experimental data and then used to predict the possible formation of troublesome side products and by-products including CCl4 and HCl. The removal of methane could be maintained with a peak removal efficiency &gt;98 % for ambient levels of methane at a flow rate of 7.5 mL min−1 with [Cl2] at 50 ppm. These tests show that our method is a viable option for continuous methane scrubbing. Additional measures may be needed to avoid complications due to the introduction of Cl2 and formation of HCl. Note that the method will also oxidize most other common volatile organic compounds. The system was tested in combination with a cavity ring-down methane spectrometer, and the developed method was shown to be successful at removing methane interference.

Temporal Variability of Surface Reflectance Supersedes Spatial Resolution in Defining Greenland’s Bare-Ice Albedo

Ice surface albedo is a primary modulator of melt and runoff, yet our understanding of how reflectance varies over time across the Greenland Ice Sheet remains poor. This is due to a disconnect between point or transect scale albedo sampling and the coarser spatial, spectral and/or temporal resolutions of available satellite products. Here, we present time-series of bare-ice surface reflectance data that span a range of length scales, from the 500 m for Moderate Resolution Imaging Spectrometer’s MOD10A1 product, to 10 m for Sentinel-2 imagery, 0.1 m spot measurements from ground-based field spectrometry, and 2.5 cm from uncrewed aerial drone imagery. Our results reveal broad similarities in seasonal patterns in bare-ice reflectance, but further analysis identifies short-term dynamics in reflectance distribution that are unique to each dataset. Using these distributions, we demonstrate that areal mean reflectance is the primary control on local ablation rates, and that the spatial distribution of specific ice types and impurities is secondary. Given the rapid changes in mean reflectance observed in the datasets presented, we propose that albedo parameterizations can be improved by (i) quantitative assessment of the representativeness of time-averaged reflectance data products, and, (ii) using temporally-resolved functions to describe the variability in impurity distribution at daily time-scales. We conclude that the regional melt model performance may not be optimally improved by increased spatial resolution and the incorporation of sub-pixel heterogeneity, but instead, should focus on the temporal dynamics of bare-ice albedo.

The role of profiling of drugs, psychotropic substances and precursors in combating their illegal trafficking

Recently, there is a negative trend in the world – increasing number of synthetic drugs, psychotropic substances and precursors in the illicit trafficking of these substances. Specially equipped underground laboratories for their drug production are being set up to meet the demand for synthetic drugs. Synthetic drugs and psychotropic substances produced in underground laboratories can be synthesized in various ways. Various precursors and reagents are used for their synthesis, which leads to the appearance of impurities in the final product. Impurities help to determine the ways of synthesis of the illegal substance, the origin of the precursors, provide information about the location of production. Due to the presence of impurities, the connections between the removed substances are revealed. Specific impurities are used to determine the route of production, which, combined with other forms of investigation, will help to link different batches of a prohibited substance to the specific person who manufactured them. Impurities associated with the synthesis of substances seized in illegal laboratories are so-called marker compounds. They are a kind of marks that guide the expert chemist on the specific method used by criminals to obtain the substance. Marker compounds are of the greatest importance for the accurate establishment of the synthesis method. Marker compounds are determined by impurity profiling of samples of the prohibited substance. The main purpose of the profiling of impurities is to assist law enforcement agencies in combating the illicit manufacture and circulation of controlled substances. The results of research and information on the circumstances of the confiscation should be recorded in the relevant created electronic databases. In the profile database, two samples of a substance with a similar chemical profile can be linked together from the manufacturing stage to the distribution stage. Data on impurity profiles and fillers can be used to estimate the batch size, time and area of drug distribution. Databases are needed for use by law enforcement agencies in operational and investigative work. Databases are needed for the timely detection and liquidation of underground drug laboratories. The above aspects emphasize the importance of cooperation between investigative, operational services and forensic agencies in the process of effective detection and cessation of crimes related to the distribution of controlled substances.

Determination of the degree of degradation of specific impurity B contained in the substance of the drug «Lomustine» by high-resolution HPLC–MS/MS method

A high-resolution HPLC–MS/MS method was proposed for the study of solutions of standards of specific impurity B contained in the substance of the drug «Lomustine», which is included in the List of Vital Medicines. A characteristic degradation product of specific impurity B, the content and quantity of which is not regulated by the European Pharmacopoeia, has been found.

Ammonia as a carrier for hydrogen production by using lanthanum based perovskites

LaNiO3 and LaCoO3 perovskites synthesized by self-combustion were characterised and studied in the ammonia decomposition reaction for obtaining hydrogen. Both the fuel to metal nitrates molar ratio and calcination temperature were found to be crucial to synthesize perovskites by self-combustion. Moreover, generating non-precursor species during synthesis and small metal size were two factors which significantly influenced catalytic activity. Hence, with a citric acid to metal nitrates molar ratio equal to one a LaNiO3 perovskite was obtained with suitable physicochemical properties (specific surface area, lower impurities, and basicity). In addition, a lower calcination temperature (650 °C) resulted in small and well-dispersed Ni0 crystallite size after reduction, which in turn, promoted the catalytic transformation of ammonia into hydrogen. For cobalt perovskites, calcination temperature below 900 °C did not have a significant influence on the size of the metallic cobalt crystallite size. The nickel and cobalt perovskite-derived catalysts, calcined at 650 °C and 750 °C, respectively, yielded excellent H2 production from ammonia decomposition. In particular, at 450 °C almost 100% of the ammonia was converted over the LaNiO3 under study. Furthermore, these materials displayed admirable performance and stability after one day of reaction.

Design of experiments in optimization and validation of hydrophilic interaction liquid chromatography method for determination of amlodipine besylate and its impurities

Abstract A new and rapid hydrophilic interaction liquid chromatographic method has been developed for the quantitative analysis of amlodipine besylate and its specific impurities (D, E, and F). For development of this method, a systematic approach which includes Design of Experiments methodology was applied. For the method optimization, Box–Behnken design and specific way Derringer's desirability function were applied. They provided identification of the optimal chromatographic conditions on the basis of obtained mathematical models and graphical procedures (three D graphs). The optimal chromatographic conditions were the analytical column ZORBAX NH2 (250 × 4.6 mm, 5 µm particle size); mobile phase consisted of acetonitrile-water phase (50 mM ammonium acetate, pH adjusted to 4.0 with glacial acetic acid) (90.5:9.5 v/v); column temperature 30 °C, mobile phase flow rate 1 mL min−1, wavelength of detection 230 nm. As other validation parameters were also found to be suitable, the possibility to apply the proposed method for the determination of amlodipine besylate and its impurities in any laboratory under different circumstances has been proven.

N-Nitrosodimethylamine (NDMA) Formation from Ranitidine Impurities: Possible Root Causes of the Presence of NDMA in Ranitidine Hydrochloride.

N-Nitrosodimethylamine (NDMA) is a probable human carcinogen. This study investigated the root cause of the presence of NDMA in ranitidine hydrochloride. Forced thermal degradation studies of ranitidine hydrochloride and its inherent impurities (Imps. A, B, C, D, E, F, G, H, I, J, and K) listed in the European and United States Pharmacopeias revealed that in addition to ranitidine, Imps. A, C, D, E, H, and I produce NDMA at different rates in a solid or an oily liquid state. The rate of NDMA formation from amorphous Imps. A, C, and E was 100 times higher than that from crystalline ranitidine hydrochloride under forced degradation at 110 °C for 1 h. Surprisingly, crystalline Imp. H, bearing neither the N,N-dialkyl-2-nitroethene-1,1-diamine moiety nor a dimethylamino group, also generated NDMA in the solid state, while Imp. I, as an oily liquid, favorably produced NDMA at moderate temperatures (e.g., 50 °C). Therefore, strict control of the aforementioned specific impurities in ranitidine hydrochloride during manufacturing and storage allows appropriate control of NDMA in ranitidine and its pharmaceutical products. Understanding the pathways of the stability related NDMA formation enables improved control of the pharmaceuticals to mitigate this risk.

The Effect of Incorporating Industrials Wastewater on Durability and Long-Term Strength of Concrete.

Concrete, as one of the essential construction materials, is responsible for a vast amount of emissions. Using recycled materials and gray water can considerably contribute to the sustainability aspect of concrete production. Thus, finding a proper replacement for fresh water in the production of concrete is significant. The usage of industrial wastewater instead of water in concrete is considered in this paper. In this study, 450 concrete samples are produced with different amounts of wastewater. The mechanical parameters, such as slump, compressive strength, water absorption, tensile strength, electrical resistivity, rapid freezing, half-cell potential and appearance, are investigated, and a specific concentration and impurities of wastewater that cause a 10% compressive strength reduction were found. The results showed that the usage of industrial wastewater does not significantly change the main characteristics of concrete. Although increasing the concentration of wastewater can decrease the durability and strength features of concrete nonlinearly, the negative effects on durability tests are more conspicuous, as utilizing concentrated wastewaters disrupt the formation of appropriate air voids, pore connectivity and pore-size distribution in the concrete.

Повышение эффективности системы мониторинга атмосферного воздуха в городе Севастополе

This article summarizes the obtained results of assessing the effectiveness of monitoring of atmospheric air pollution in the city of Sevastopol by stationary and mobile sources and gives recommendations for its improving. Analysis of the existing air monitoring network shows that the monitoring system needs to be modernized due to a number of identified inconsistencies: the number of stationary posts in the city of Sevastopol does not meet the requirements of RD 52.04.186-89 and their number should be increased; the location of stationary posts does not allow obtaining an objective picture of air pollution in all areas of the city; the list of specific impurities subject to control requires clarification and justification based on the available data on the actual intake of pollutants into the city atmosphere; the location of checkpoints on highways does not cover all highways in the city. A list of the largest stationary pollution sources is compiled. Maximum permissible emissions of 243 enterprises are analyzed, including information on 1482 sources of emissions. The main sources of air pollution are revealed and their ranking by gross emissions is performed. An assessment of the data of field observations of atmospheric air pollution in the city of Sevastopol for compliance with the current standards is carried out and a preliminary list of pollutants is formulated to justify the expediency of their control at stationary and route points of the city. The article describes some aspects of a large-scale study aimed at assessing the effectiveness of the air pollution monitoring in the city of Sevastopol. Other stages of research and proposals for modernizing the monitoring system are planned to be published in a series of subsequent articles.

Application of a Semiautomated Crystallizer to Study Oiling-Out and Agglomeration Events—A Case Study in Industrial Crystallization Optimization

A case study on a challenging industrial crystallization is presented. The crystallization under investigation was prone to oiling-out, which led to agglomeration and stalling of crystallization. A semiautomated crystallizer—designed and built iteratively as the crystallization needs changed—was used to study the crystallization and identify the failure modes. A fiber optic probe was included in this setup to track turbidity, which was found to drop in signal whenever an oiling-out/agglomeration event was observed with in situ video microscopy. With this knowledge, the turbidity was monitored to detect oiling-out and was subsequently used as a feedback mechanism to change the temperature profile to reverse oiling-out and resume crystal growth during the crystallization. The automated sampler, coupled with off-line HPLC analysis, provided valuable insight about the behavior of impurities during oiling-out and identified one specific impurity that influenced the formation of the second liquid phase and crystallization rate. The data-rich experimentation performed enabled the expedient optimization of crystallization parameters such as the temperature profile, seed loading, and cycle time. The final crystallization was robust, predictable, and capable of self-correction should a potential failure mode be encountered.

Quantum transport properties of gas molecules adsorbed on Fe doped armchair graphene nanoribbons: A first principle study

Graphene, when doped with transition metals, is considered, both experimentally and theoretically, as a good candidate for the detection of gas molecules as CO, CO2, NO or NO2. This opens new perspectives for gas sensor set-ups considering that devices based on 2 dimensional graphene are more sensitive to detect molecules than solid-state gas sensors. The state of the arts on gas adsorption on Fe doped armchair graphene nanoribbons (Fe-AGNR) is still in its starting phase and thorough investigations of the mechanism of the adsorption on graphene need to be done. In the present work, the electronic and transport properties of molecules adsorbed on Fe-AGNR are scrutinized using ab-initio calculations. We observe that the adsorption of gas molecules on Fe-AGNR changes significantly the electronic properties of both the valence and the conduction band. Besides, The adsorbed molecules change the local electron density of states of the graphene nanoribbons, modifying thus the conductivity, being one of the main output quantity of the gas sensors. We also observe that the adsorbed molecules induce specific impurity bands which play a role in the transport properties. Finally, considering the observed variations of electrical conductance induced by the molecules, we propose several strategies to set-up gas sensors for CO, CO2, NO and NO2 molecules. These strategies are either based on the measurement of the conductance in the valence or the conduction band (using either p or n-doped Fe-AGNR) or to the spin polarization induced by the NO and NO2 molecules.

Investigating the chemical impurity profiles of fentanyl preparations and precursors to identify chemical attribution signatures for synthetic method attribution

From an analytical chemistry standpoint, determining the chemical attribution signatures (CAS) of synthetic reaction mixtures is an impurity profiling exercise. Identifying and understanding the impurity profile and CAS of these chemical agents would allow them to be exploited for chemical forensic information, such as how a particular chemical agent was synthesised. Being able to determine the synthetic route used to make a chemical agent allows for the possibility of batches of the agent, and individual incidents using that agent, to be forensically linked. This information is of particular benefit to agencies investigating the nefarious and illicit use of chemical agents. One such chemical agent of interest to law enforcement and national security agencies is fentanyl. In this study two acylation methods for the final step of fentanyl production, herein termed the Janssen and Siegfried methods, were investigated by liquid chromatography- high resolution mass spectrometry (LC-HRMS) and multivariate statistical analysis (MVA). From these data, fifty-five chemical impurities were identified. Of these, ten were specific CAS for the Janssen method, and five for the Siegfried method. Additionally, analytical data from four different literature methods for production of the fentanyl precursor 4-anilino-N-phenethylpiperidine (ANPP), were compared to the results obtained from the method of production (Valdez) used in this study. Comparison of the LC-HRMS data for these five methods allowed for four Valdez specific impurities to be identified. These may be useful CAS for the Valdez method of ANPP production.

Physical and chemical properties of tigernut oil as influenced by variety and method of extraction

This study was carried out to investigate the physical and chemical properties of tigernut oil as influenced by variety and methods of extraction. Oil was extracted from yellow and brown varieties of tigernut using mechanical screw press and N-hexane, and it was characterized for physical and chemical composition. The moisture content, acid value, free fatty acid, iodine value, saponification value and peroxide value for tigernut oil from extraction methods ranged from 2.97 to 3.30%, 0.28 to 0.56mgKOH/g, 0.55 to 1.12g/100g, 66.11 to 69.75gI/100g, 174.93 to 210.06mgKOHg and 0.27 to 0.56MgH2O2, respectively. The range of values for specific gravity, percentage impurity, cloud point, smoke point and melting point are: 0.64 to 0.99g/ml, 0.15 to 0.24%, 9.00 to 25.5°C, 170.5 to 204.5°C and 18.0 to 28.5°C, respectively. However, the study showed that both the physical and chemical composition of tigernut oil were affected by the extraction methods used in this study.

Technology for gadolinium-based ultra-low-background compounds. Part 1. Studies of the impurity composition of gadolinium-containing compounds for determination of promising raw materials

The purpose of this work was to identify promising raw materials for creating composite materials that effectively capture neutrons in experiments on the study of rare physical processes. Such composites are made on the basis of a polymer matrix impregnated with gadolinium. In this case, the intrinsic radioactive background of the composite, determined primarily by the residual content of uranium and thorium, should be no more than 100 &mu;Bq/kg, which, in terms of the concentration in the materials, is no more than 1&middot;10&ndash;9 % (wt.) for U and 2,5&middot;10&ndash;9 % (wt.) for Th. In the study of ten commercial inorganic gadolinium-containing compounds (oxide, chloride, sulfate, nitrate) using inductively coupled plasma mass spectrometry (ICP-MS), a method was developed for determination of 65 impurity elements with a detection limit of 10&ndash;5&ndash;10&ndash;9 % (wt.) depending on the specific impurity. It is shown that when analyzing gadolinium-containing compounds by the ICP-MS method for the quantitative measurement of concentrations of difficult-to-detect elements, it is recommended to use the following isotopes: 82Se, 147Sm, 151Eu, 163Dy, 178Hf, 188Os, 194Pt. The detection limit for impurities making the greatest contribution to the residual radioactivity was reduced to 1.1&middot;10&ndash;9 % (wt.) for U and to 1.6&middot;10&ndash;9 % (wt.) for Th. It was found that the content of U and Th depends more on the genesis of the raw materials from which the gadolinium-containing compounds were obtained than on the general chemical purity of the compounds, which varied from 99.45 to 99.9994% (wt.) in the samples under study. The lower content of U and Th is observed in gadolinium-containing compounds obtained from the secondary raw materials (extraction phosphoric acid) or from mineral raw materials formed in sedimentary rocks (phosphogypsum). It is these compounds that should be considered as the most promising raw materials for development of the technology of the gadolinium-based ultralow-background compound, which is used as a neutron-absorbing additive in detectors and structural composite materials.This work was supported by the Ministry of Science and Higher Education&nbsp;of the Russian Federation, unique project identifier RFMEFI60419X0238.

Formation of an Unprecedented Impurity during CE-SDS Analysis of a Recombinant Protein.

The main purposes of this article are to describe an unprecedented phenomenon in which significant amount of a shoulder peak impurity was observed during normal non-reducing capillary electrophoresis-sodium dodecyl sulfate (CE-SDS) analysis of a recombinant fusion protein X, and to evaluate the root cause for this phenomenon. A series of experiments were conducted to study the nature of this degradation. Effects of iodoacetamide (IAM), heating temperature, duration, and SDS on the formation of this specific impurity were evaluated using a variety of characterization techniques. The formation of the impurity as observed in CE-SDS was actually due to alkylation of lysine and serine residues with IAM, as confirmed by peptide mapping and LC-MS/MS, which increased the molecular weight and therefore decreased the electrophoretic mobility. The amount of impurity was also strongly dependent on sample preparation conditions including the presence or absence of SDS. Our study clearly suggested that even though IAM has been used extensively as an alkylation reagent in the traditional non-reducing CE-SDS analysis of monoclonal antibodies and other proteins, alkylation with IAM could potentially lead to additional impurity peak, and therefore complicating analysis. Therefore, before performing CE-SDS and other analyses, the effects of sample preparation procedures on analytical results must be evaluated. For protein X, IAM should be excluded for CE-SDS analysis.