Analysis Of Impurities Research Articles

Universal response method for accurate quantitative analysis of the impurities in quinolone antibiotics using liquid chromatography coupled with diode array detector and charged aerosol detector

HPLC method is the standard method for the separation and quantification of impurities from quinolone antibiotics. However, due to the large differences in the UV absorption of the impurities in quinolone antibiotics, quantitative analysis without the availability of corresponding reference substances currently poses a challenge. A sensitive and direct method using high performance liquid chromatography coupled with diode array detector and charged aerosol detector (HPLC-DAD-CAD) was developed for the analysis of impurities in quinolone antibiotics. The chromatographic conditions were optimized for good separation and output signal of CAD detector by response surface method (RSM). The systematic variation of CAD parameter settings, such as nebulization temperature, filter constant and power function value (PFV), were used to study the effect of on the detector response of signal-to-noise ratios (S/N) and linearity for ofloxacin, ciprofloxacin and their impurities. In the method validation, good linearity of each component was obtained with coefficient of determination (r) greater than 0.999 in the range of 0.5–300 μg mL−1. The average recoveries of each component were 99.02–102.39 % by DAD, were 98.22–101.91 % by CAD, RSDs were less than 2.5 % for intra-day and inter-day precision by DAD-CAD, with good precision and accuracy. The correction factor experimental results showed that the developed method provided a uniform response to the impurities with differences chromophores and could unbiasedly and directly detect the impurities in quinolone antibiotics. The method is first reported application of HPLC-DAD-CAD method for the analysis of impurities in quinolone antibiotics and it can be used for quality control of quinolone antibiotics.

Development and Application of a Validated HPLC Method for the Determination of Alpelisib and its Process-Related Impurities in Pure Drug and Pharmaceutical Formulations

Impurity analysis plays a significant role in the manufacture of a safe pharmaceutical product that ensures the safety of consumers. Keeping this in consideration, the present study was intended to develop a simple and sensitive HPLC method for the resolution and quantification of 4 process-related impurities namely impurities 1, 2, 3 and 4 in alpelisib pure drug and formulations. The method consumes greener solvents as a mobile phase that resolves the analytes on ProntoSIL ODS-C18 (250×4.6 mm; 5 μ id) column at room temperature as stationary phase, ethanol and 0.1% aqueous acetic acid in 65:35 (V/V) at pH 4.5 as mobile phase at 0.8 mL/min flow rate, UV detection at 246 nm. The method can detect the analytes at retention times of 7.05, 4.52, 6.09, 2.88 and 8.14 min respectively for alpelisib, impurity 1, 2, 3 and 4. The analysis was completed with a run time of 15 min that consume less solvent and the same analysis time. The linearity of the proposed method was perceived in the range of 12.5 to 100 μg/mL for alpelisib and 0.0125 to 0.10 μg/mL for impurities. The method can effectively resolve the unknown stress degradation products generated during the stress exposure of alpelisib along with its known impurities in the study. The outcomes of other validation studies were likewise satisfactory and proven adequate for regular analysis of alpelisib and its process-related impurities in bulk drug and pharmaceutical tablet doses.

Impurity analysis of electroplated gold components with multi-layered structures by thermal desorption spectrometry toward application in gold Micro electro mechanical system capacitive accelerometers

Au-based micro-electro-mechanical-system (Au-MEMS) capacitance accelerometers show high sensitivity by suppressing the mechanical noise because of the high mass density of gold (ρ = 19.3 g/cm3). On the other hand, their long-term reliability suffers from drift phenomena induced by the impurities incorporated in the key component during their fabrication process, such as the gold electroplating step. Herein, impurities in electroplated Au-based components for MEMS capacitive accelerometers are evaluated by thermal desorption spectrometry (TDS) measurements. The TDS measurement reveals that dominant desorption gases from the Au-based component are molecular hydrogen (H2) and water (H2O). These desorption gases are derived from impurities in the electroplated Au-based component, and the amount of these gases is significantly suppressed by a thermal treatment step. In conclusion, this study demonstrates that the electroplated Au-based component contains impurities originated from the fabrication process, and these impurities could be removed by a thermal treatment step.

Changes in methamphetamine impurity profiles induced by tert-butoxycarbonylation.

Analysis of impurities in methamphetamine (MA) can be used to characterize MA seizures, investigate the relationship among MA seizures, and provide information on their synthetic routes. Recently, chemically derivatized MA, such as tert-butoxycarbonyl (t-Boc) MA, has been seized and attracted attention because routine forensic analysis methods may fail to correctly identify them. Chemical derivatization is a simple method for protection and deprotection of a compound, and protection of MA using t-Boc can be used to mask the MA. Although t-Boc derivatization might alter the impurity profile of MA, the actual changes in the impurity profile have not been investigated. In this study, changes in the MA impurity profile with tert-butoxycarbonylation were explored. MA and some typical impurities were derivatized using di-tert-butyl dicarbonate and water. Analysis of the impurities in five MA samples by gas chromatography showed that peaks both appeared and disappeared for the deprotected MA compared with the original MA. However, typical impurities important for characterizing MA seizures were conserved after derivatization and deprotection. Most of the new peaks were speculated to be contaminants introduced during derivatization and deprotection. A peak giving a mass spectrum similar to that of t-Boc MA was detected in the chromatograms of t-Boc MA and deprotected MA. Although the origin of this peak was not determined, it might be a marker for the MA involving tert-butoxycarbonylation. These results indicate that tert-butoxycarbonylation can alter the MA impurity profile; therefore, care is needed when interpreting results for derivatized MA.

Direct Analysis of Si, SiC and GaN Wafers by LA-GED-MSAG-ICP-MS

The new laser ablation technique has been developed for analysis of metallic impurities in SiC and GaN wafers. Particles generated by a femto-second laser ablation were aspirated by an ejector and introduced to an Inductively Coupled Plasma Mass Spectrometry (ICP-MS) via a Gas Exchange Device (GED) and analyzed. A Metal Standard Aerosol Generation (MSAG) was used for quantitation of metallic impurities in SiC and GaN wafers.

Identification and Determination of Impurities in a New Therapeutic Agent for Fatty Liver Disease.

Methyl 7,7'-dimethoxy-5'-(morpholinomethyl)-[4,4'-bibenzo[d][1,3] dioxole]-5-carboxylate methanesulfonate (IMM) is an innovative drug for the treatment of nonalcoholic fatty liver disease (NAFLD) owing to its high efficacy and low toxicity. In this study, five minor impurities (I, II, III, IV, and V) were identified and analyzed using spectroscopic evidence, chemical synthetic methods, and liquid chromatography-tandem mass spectrometry (LC-MS/MS). The impurities included hydrolysates and oxidation by-products extracted from both the drug in its final formulation and during synthesis. Toxicity prediction revealed potential carcinogenicity of impurity V containing an N-oxygen fragment. A reliable and selective HPLC method for the quantitative analysis of impurities I-IV and a sensitive HPLC-MS/MS method for potential genotoxic impurity V were developed and optimized. The methods were validated based on the International Council for Harmonization guidelines. Satisfactory linearity was obtained for the analytes over the range of 0.1-2.0 μg/mL for impurities I-IV and 0.3-30.0 ng/mL for impurity V, and in all cases, the fitting correlation coefficients exceeded 0.999. The obtained limits of detection values were 0.05 ng/mL and 0.005 μg/mL for impurity V and impurities I-IV, respectively. The precision and repeatability of the methods were less than 1.08% and 8.72% for each impurity. The recovery percentages of all impurities were in the range of 91.18%-111.27%, with the relative standard deviation of less than 3.69%. The greenness assessment of the HPLC method and the HPLC-MS/MS method were evaluated by using AGREE software with a score value of 0.72 and 0.68, respectively. The recommended procedures that were accurate, specific, and ecofriendly were applied to the existing active pharmaceutical ingredients of IMM, and they generated satisfactory results.

State-of-the-art and challenges in the analysis of renewable gases.

The development of renewable and low-carbon gases for injection into the gas grid obtained by different processes such as anaerobic digestion, pyrogasification, hydrothermal gasification, and methanation, followed by upgrading steps, increases the demand for analysis and characterization in order to fully manage their integration into the gas value chain. If the analysis of the main compounds (methane, carbon dioxide, hydrogen, and carbon monoxide) is well described, the analysis of impurities in renewable gases remains more challenging due to their various natures and quantities. After a brief description of renewable and low-carbon methane production processes, the review focuses on the methods used for the analysis of the different compounds in renewable gases, from the main ones to impurities at ppbv levels. Gas chromatography (GC), coupled with different detectors, is the preferred technique, enabling the analysis and quantification of siloxanes, terpenes, oxygenates, and sulfur compounds. Recently, comprehensive two-dimensional GC has been applied to renewable gases, increasing the number of compounds detected. Non-chromatographic techniques are also reviewed. As sampling is of major importance in the search for reliable analyses, a whole section is devoted to this aspect. Among the available methods, pre-concentration on adsorbent tubes emerges as the most relevant solution.

Analysing Impurities and Degradation Products

In the realm of pharmaceutical analysis, the analysis of impurities and degradation products takes centre stage, and its significance cannot be overstated. These undesired substances can profoundly impact the quality, safety and efficacy of pharmaceutical products, necessitating rigorous analytical methods and processes at every stage of drug development and manufacturing. Forced degradation studies are instrumental in identifying and characterizing impurities that may arise within a product, a pivotal source of information for quality control and regulatory compliance. Stability testing is integral to the batch release process, ensuring each product batch meets established stability criteria before entering the market. Stability testing and degradation studies are indispensable constituents of pharmaceutical analysis. They substantially contribute to preserving the quality, safety, and efficacy of pharmaceutical products. Beyond their regulatory mandates, these studies serve as proactive instruments for comprehending and supervising product stability across their life cycles. The insights gleaned from these endeavours inform critical judgments during drug development and manufacturing, ultimately assuring the welfare of patients and compliance with stringent regulatory requisites.

Development of a Suitable HPLC Method for the Analysis of Impurities in Clorprenaline and Bromhexine Capsules and Identification of Unknown Impurities by 2D LC-Q-TOF MS

Background: Impurities may reduce antibacterial activity and affect clinical efficacy, However, there has been no report on the impurity of clorprenaline and bromhexine capsules. Objective: In order to determine the impurities in compound clorprenaline and bromhexine capsules. Methods: A new stability-indicating HPLC method was established. A Boston Green ODS column was used, and the UV detection was 225nm. Results: The established method was highly specific, sensitive, accurate, and suitable for routine quality control of clorprenaline and bromhexine capsules. The structures of unknown impurities were characterized by the MS/MS data. Conclusion: These results provide a sufficient basis for our subsequent study on the safety of Compound Clorprenaline and Bromhexine Capsules and also provide ideas for the impurity research of other compound preparations.

Universal response method for the quantitative analysis of photodegradation impurities in lomefloxacin hydrochloride ear drops by liquid chromatography coupled with charged aerosol detector

In terms of risk assessment especially for the impurities with different ultraviolet responses, quantitative analysis without the availability of corresponding reference substances currently poses a challenge. In this study, a universal response method was established for the quantitative analysis of photodegradable impurities in lomefloxacin hydrochloride ear drops by high performance liquid chromatography-charged aerosol detector (HPLC-CAD) for the first time. The chromatographic conditions and CAD parameters were optimized for a good separation and sensitivity. The uniform response of developed method was validated by impurity reference substances with different ultraviolet responses. In the gradient compensation HPLC-CAD method validation, good linearities were obtained with coefficient of determination (R2) all greater than 0.999 for lomefloxacin and impurity reference substances. The average recoveries of the impurities were 98.63%− 102.18% by UV and 97.92%− 102.57% by CAD, respectively. RSDs all were less than 2.5% for intra-day and inter-day precision by UV and CAD, with good precision and accuracy. The correction factor experimental results showed that the developed method provided a uniform response to the impurities with differences chromophores in lomefloxacin. The effects of packaging materials and excipients on the photodegradation were also investigated using the developed method. The results of correlation analysis showed that the packaging materials with low light transmittance and the organic excipients (glycerol and ethanol) could significantly improve the stability of lomefloxacin hydrochloride ear drops. The developed HPLC-CAD quantification method was a reliable and universal response method for quantitative analysis of impurities in the lomefloxacin. This study also revealed the key factors affecting the photodegradation of lomefloxacin hydrochloride ear drops, which guided enterprises to improve drug prescription and packaging materials and ensure the public medication safety.

Impurity Analysis of 5.5 N Nitrogen Gas and Its Impact on the Preparation of Class I Type Calibration Gas Mixtures

AbstractKnowledge of impurities in matrix gas is one of the critical requirements for the preparation of class I type calibration gas mixtures (primary reference gas mixtures, PRGMs) as per ISO 6142‐1. PRGMs are prepared gravimetrically using high‐purity component gas and high‐grade nitrogen, here 99.9995 % (5.5 N) as matrix gas. In this study, quantification of gaseous impurities such as moisture (H2O), methane (CH4), and carbon monoxide (CO) in 5.5 N nitrogen is performed using CRDS (cavity ring down spectroscopy). Carbon dioxide (CO2) and total hydrocarbons (THC) are analyzed using gas chromatography flame ionization detector (GC‐FID), while the determination of nitrogen dioxide (NO2) impurity is conducted colorimetrically using a UV‐Vis spectrophotometer. Total impurities in 5.5 N nitrogen are found to be (2945±21.5) ppb. The impact of utilizing this nitrogen is examined through the stability study of ambient range binary component gas mixtures of CH4 and CO in nitrogen and found that 5.5 N nitrogen can be used as matrix gas for preparing PRGMs of CH4 and CO. However, the component gas impurity present in nitrogen potentially affect the accuracy of gravimetrically prepared gas mixture.

Shortening synthesis process of zirconium hydroxide as a hydrolysis product of sodium zirconate

This research was focusing on shortening the process of Zirconium hydroxide (Zr(OH)<sub>4</sub>) synthesis to get a more efficient process. In the earlier method, Zr(OH)<sub>4</sub> was produced through ZOC, which was the product of Na<sub>2</sub>ZrO<sub>3</sub> reacted with HCl. While this study offers a new method to synthesize Zr(OH)<sub>4</sub> through the hydrolysis process of sodium zirconate (Na<sub>2</sub>ZrO<sub>3</sub>), removing the leaching step of Na<sub>2</sub>ZrO<sub>3</sub> with HCl. The hydrolysis process of Na<sub>2</sub>ZrO<sub>3</sub> was carried out in a multistage stirred reactor at 70 °C. The multistage hydrolysis process occurred in 13 stages with 4000 grams of feed and 890 liters of water. This process produced 2500 grams of Zr(OH)<sub>4</sub>. Then the impurities analysis was done using UV-Vis and atomic absorption spectroscopy (SAA). The UV-Vis analysis was done to analyze Si concentration, while the atomic absorption spectroscopy (SAA) was done to analyze Na concentration. Si and Na concentrations could decrease to 23.98 µg/ml and 1.05 µg/ml, respectively. The Zr(OH)<sub>4</sub> contained in the residue was characterized using X-Ray Diffractometer (XRD) and Fourier Transform Infrared Spectroscopy (FTIR). Then, the calcination process of Zr(OH)<sub>4</sub> was done at 300 °C and 400 °C for 1 hour, and characterized using XRD. The XRD result shows crystals of zirconium titanium oxide or srilankite, and SiO<sub>2</sub> crystals that are separated from ZrO<sub>2</sub> or TiO<sub>2</sub> crystals. Surface analysis was done using Scanning Electron Microscope – Energy Dispersive X-Ray (SEM-EDX), the result shows that the hydrolysis process at the 3<sup>rd</sup>, 7<sup>th</sup>, and 13<sup>th</sup> stages have different amorphous crystals with bright colors. At the 13th hydrolysis stage, Zr concentration increased to 63.38%, and Si concentration decreased. Thus, the shorter process of Zr(OH)<sub>4</sub> synthesis has been done successfully.

Quantitative analysis of tungsten in steel by one-point calibration laser-induced breakdown spectroscopy in vacuum

Laser-induced breakdown spectroscopy (LIBS) has been proposed as a promising in-situ diagnostic approach for the elemental analysis of the co-deposition impurities on plasma-facing components (PFCs) of the experimental advanced superconducting tokamak (EAST) as well as ITER tokamak. The EAST has been equipped with an ITER-like tungsten (W) divertor, and impurities of W originating from divertor erosion can be transported into core plasma as impurities, which seriously reduces the plasma performance with power radiation losses and fuel dilution. In the present work, to achieve a more reliable quantitative analysis, a variation of the CF-LIBS algorithm, the so-called one-point calibration LIBS (OPC-LIBS), is examined for major and minor constituents in a set of W-Mo-Fe-Cr steel samples (chosen as a proxy of the co-deposition layers on the lower hybrid wave gas puffing pipe of EAST) at 5 × 10−5 mbar. The OPC-LIBS essentially employs one matrix-matched standard sample of known composition to evaluate the comprehensive correction factors of crucial experimental and spectroscopic parameters. These are essential for empirically correcting the LIBS line intensities to achieve a more precise quantitative analysis compared with the conventional CF-LIBS. In the case of OPC-LIBS measurement in vacuum, the relative error of major elements such as Fe (85.24–88.69a.t.%) is below 1.64%, while that of minor elements like W (1.91–6.27a.t.%) is within 24.79%. It is substantially better than the predicted results of CF-LIBS, in which the relative error of Fe and W in order are within 10.75% and 202.03%. The obtained results confirm the quantitative analysis capability of the OPC methodology in a tokamak environment for the in-situ LIBS system.

Thrombogenic potential of picomolar coagulation factor XIa is mediated by thrombin wave propagation.

Inhibitors of coagulation factor XIa (FXIa) are currently being investigated as potential anticoagulant therapies. We hypothesize that circulating FXIa could be a potential target for these therapies. Using previous analyses of FXIa impurities in immune globulin products involved in thrombotic adverse events, we estimated that picomolar levels of FXIa can be thrombogenic. In an invitro clot-growth assay, 0.1-3 pM of FXIa did not, by itself, activate clotting but increased the size of growing clots. Spatio-temporal reconstruction of thrombin activity inside the clot revealed that FXIa's effect was limited to the clot-plasma interface, in which FXIa produced a taller than standard wave of thrombin. Factor-depleted plasma and a panel of selective anti-FXIa antibodies showed that exogenous FXIa effects are (1) blocked by anti-FXIa antibodies, (2) independent of FXI activation inside the clot, and (3) larger than the contribution of in situ FXIa. In a thrombin generation (TG) assay, picomolar FXIa did not initiate TG but rather promoted TG triggered by tissue factor or thrombin, suggesting that the effect of FXIa on the thrombin wave is mediated by the elevation of thrombin-triggered TG. In circulating bovine blood, low doses of human FXIa did not initiate clotting but increased the size of stenosis-triggered thrombi. FXIa injection in mice enhanced TG in plasma for at least 6 hours exvivo, confirming the persistence of circulating FXIa. Our findings suggest that picomolar levels of circulating FXIa may not be able to initiate thrombosis but can facilitate thrombus growth through the facilitation of TG inside the clot.

Exploring the dynamic growth of sugar crystals: A volume diffusion non-steady state model under variable conditions

Observing the effect of temperature, concentration, and impurity on the crystal growth rate is accomplished by simulating the growth of sugar crystals. The volume diffusion growth model was used to examine the crystallization process and compare the effect of the three parameters on the growth of sugar crystals. The non-steady-state behavior of the process is examined using MATLAB simulation. A disturbance analysis of temperature, concentration, and impurity has been conducted to demonstrate their impact on the final crystal size of sugar. The findings show that temperature and impurities affect the final sugar crystal size. In addition, the size of crystals can be enhanced by increasing the concentration of sugar solution.

Challenges of Impurities Analysis in Manufacturing Therapeutic Oligonucleotides

Challenges of Impurities Analysis in Manufacturing Therapeutic Oligonucleotides

Purification and Improved Photoelectric Properties of Lead-Free Perovskite Cs3Bi2Br9 Crystals

The lead-free halide perovskite Cs3Bi2Br9 is a promising semiconductor material for room-temperature X-ray detection due to its excellent properties. However, material purity and crystal quality still limit the use of Cs3Bi2Br9 crystals as detectors. In this work, we present a highly efficient purification method using continuous vacuum extraction to sublimate BiBr3 precursors for Cs3Bi2Br9. Impurity analysis via inductively coupled plasma mass spectroscopy showed that the purification method successfully removed most of the impurities in BiBr3 precursors and improved the purity by at least one order of magnitude. Centimeter-sized Cs3Bi2Br9 single crystals were grown by the vertical Bridgman method. The improved properties after purification were confirmed by UV-Vis-NIR spectra, infrared transmittance, and current–voltage (I–V) measurements. The results showed that the average transmittance of Cs3Bi2Br9 crystals significantly increased from 62% to 75% in the 0.5–20 μm spectral range. Additionally, the resistivity increased by nearly three orders of magnitude from 5.0 × 109 Ω·cm to 2.2 × 1012 Ω·cm, meaning the material will have low leakage currents and be suitable for developing applications for room temperature radiation detection.

Novel Robust Internal Calibration Procedure for Precise FT-IR Measurements of Nitrogen Impurities in Diamonds

FT-IR spectroscopy is the basic finger-print method for qualitative and quantitative analysis of nitrogen, boron, and hydrogen impurities in natural and synthetic diamonds. In quantitative measurements of impurity concentrations, external standard samples are required for the calibration procedure during the analysis. In this study, the double-phonon mid-IR absorption coefficient of optical phonons of the diamond host matrix, the robust internal mid-IR absorption standard, was accurately measured for tens of diverse diamond samples, thus enabling precise calibrated measurements of ultra-low detectable impurity concentrations.

Development of a Primary Iridium Solution Standard Traceable to the International System of Units.

The purpose of this work was to develop a primary solution standard for iridium (Ir) that is directly traceable to the International System of Units (SI). The candidate starting material was ammonium hexachloroiridate hydrate, ((NH4)3IrCl6·3H2O), the Ir salt. The SI traceability of the Ir salt was established by the gravimetric reduction (GR) of the salt to the metal under H2. GR traces the results of the analysis directly to the SI base unit of mass, the kg. The GR was also performed on high-purity Ir metal powder, an independent source of Ir, used as a comparison material for the salt. A method for dissolving the Ir metal was developed by modifying information found in the literature. Trace metallic impurities (TMI) analysis was performed on the Ir salt using ICP-OES and ICP-MS. Inert gas fusion (IGF) analysis provided data for the O, N, and H content of the gravimetrically reduced and unreduced Ir metals. The combined results of the TMI and IGF analyses provided the purity data, a required component for the claim to SI traceability. Solution standards were gravimetrically prepared from the candidate SI traceable Ir salt. Solution standards for comparison were prepared from the dissolved, unreduced high-purity Ir metal powder. These solutions were compared by a high-precision ICP-OES method. Agreement in the results between these Ir solutions, with uncertainty estimates calculated by error budget analysis, confirmed the accuracy of the Ir assay in the candidate SI traceable Ir salt, (NH4)3IrCl6·3H2O, thus confirming the concentrations and uncertainties for the primary SI traceable Ir solution standards made from the (NH4)3IrCl6·3H2O.

Clustering of Tadalafil API Samples According to their Manufacturer in the Context of API Falsification Detection

This paper reports the results of the active pharmaceutical ingredient (API) fingerprint study, organised by the General European Official Medicines Control Laboratory Network (GEON), on tadalafil. A classical market surveillance study, evaluating compliance to the European Pharmacopoeia, was combined with a fingerprint study, the latter to obtain characteristic data for the different manufacturers, allowing the network laboratories to conduct authenticity tests for future samples, as well as to detect substandard and falsified samples.In total, 46 tadalafil API samples from 13 different manufacturers were collected. For all samples fingerprint data was collected through analysis of impurities and residual solvents, mass spectrometric screening, X-ray powder diffraction and proton nuclear magnetic resonance (1H-NMR). Chemometric analysis revealed that all manufacturers could be characterised based on the impurity, residual solvent and 1H-NMR data. Future suspicious samples in the network will therefore be analysed with these techniques in order to attribute the sample to one of the manufacturers. If the sample cannot be attributed, a more profound investigation will be necessary to reveal the origin of the sample. In cases where the suspect sample is claimed to be from one of the manufacturers included in this study, analysis can be limited to the test distinguishing that manufacturer.