Analysis Of Organic Impurities Research Articles

Analysis of Organic Impurities of Besifloxacin Hydrochloride by High-Performance Liquid Chromatography with Isocratic and Gradient Elution

Introduction: Impurity analysis is an important step in the quality control of pharmaceutical ingredients and the final product. Impurities can arise from drug synthesis or excipients and even at small concentrations may affect product efficacy and safety. In this work, two methods using highperformance liquid chromatography (HPLC) were developed and validated for the evaluation of besifloxacin and its impurity synthesis, with isocratic elution and another with gradient elution. Method: The analysis by HPLC in isocratic elution mode was performed using a cyano column maintained at 25 °C. The mobile phase was composed of 0.5% triethylamine (pH 3.0): acetonitrile (88:12 v/v) eluted at a flow rate of 1.0 mL/min with detection at 330 nm. The gradient elution method was carried out with the same column and mobile phase components only modifying the rate between organic and aqueous phase during analysis. The procedures have been validated according to internationally accepted guidelines, observing results within acceptable limits. Results: The methods presented were found to be linear in the 140 to 260 μg/ mL range for besifloxacin and 0.3 to 2.3 μg/ mL for an impurity named A. The limits of detection and quantification were, respectively, 0.07 and 0.3 μg/ mL for impurity A, with a 20 μL injection volume. The precision achieved for all analyses performed provided RSD inter-day equal to 6.47 and 6.36% for impurity A with isocratic elution and gradient, respectively. The accuracy was higher than 99% and robustness exhibited satisfactory results. In the isocratic method, an analysis time of 25 min and 15 min was obtained for the gradient. For impurity A, the number of theoretical plates in the isocratic mode was about 5000 while in the gradient mode it was about 45000, hence, it made the column more efficient by changing the mobile phase composition during elution. In besifloxacin raw material and in the pharmaceutical product used in this study, other related impurities were present but impurity A was searched for and not detected. Conclusion: The proposed methods can be applied for the quantitative determination of impurities in the analysis of the besifloxacin raw material, as well as in ophthalmic suspension of the drug, considering the quantitation limit.

Development and validation of a stability indicating HPLC method for organic impurities of erythromycin stearate tablets

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.

Estimation of synthetic route of methamphetamine samples seized in China by direct analysis in real time with high-resolution mass spectrometry and chemometric analysis of organic impurities

A direct analysis in real time combined with high-resolution mass spectrometry (DART-HRMS) method was established to quickly detect organic impurities in methamphetamine (MA) samples. A partial least-squares discriminant analysis (PLS-DA) model was established by using MA samples with known synthetic pathways, and the synthetic pathways of unknown MA were determined by the PLS-DA model. The PLS-DA model was used to analyze characteristic organic impurities, which were identified as chemical markers in different synthetic-pathway MA samples by VIP (Variable Importance for the Projection) values and p-values. Thirty organic impurities were determined by DART-HRMS. Among these compounds, 7 organic impurities had a VIP value greater than 1, which indicated specificity for the grouping, including amphetamine, 1-phenylpropan-2-one oxime, N-formylamphetamine, ephedrine/pseudoephedrine, bibenzyl, α-methyldiphenethylamine and 1,3-diphenylacetone, while 5 organic impurities played a important role in classifying three groups. Amphetamine and 1-phenylpropan-2-one oxime played an important role in the R group, which represented MA samples using 1-phenyl-2-propanone as a starting material in the reductive amination reaction. Bibenzyl was important in the N group, in which MA samples were produced by ephedrine or pseudoephedrine and the iodine /phosphorus (I/P) (Nagai, Moscow, or Hypo) method. Ephedrine/pseudoephedrine and α–methyldiphenethylamine were important in the E group, in which samples were produced by ephedrine or pseudoephedrine and the catalytic hydrogenation method. The established PLS-DA model was also used to analyse MA samples of unknown synthetic routes. This established method is simple and fast and can achieve high-throughput analysis of samples to save time and analyse more samples. The analysis results provide effective information for drug law enforcement agencies.

Physicochemical Analysis of Organic Impurities in the Coolant of Combined Heat and Power Plants Equipped with Combined-Cycle Power Installations

In 2018, combined-cycle power installations equipped with heat-recovery steam generators were commissioned at the combined heat and power plant nos. 1, 2, and 3 (CHPP-1, CHPP-2, and CHPP-3) in the city of Kazan. The content of organic substances in the blowdown water of clarifiers, in chemically demineralized water, in evaporating plant condensate, in heat-recovery steam generator feed water and blowdown water, and in turbine condensate was investigated. Organic substances in dry form were separated from water samples using the extraction method. The physicochemical properties and structures of the separated organic impurities were determined using an elemental analysis, infrared spectroscopy, high-efficient liquid chromatography, chromatography-mass spectrometry, and nuclear magnetic resonance methods. It was found that the content of total organic carbon (TOC) was higher than its standardized value in the heat-recovery steam generator feed water, slightly higher than the standardized value in the condensate of evaporators, and in compliance with the existing standard requirements in the turbine condensate and chemically demineralized water. Humic substances that are not removed from water during its pretreatment and enter in the heat-recovery steam generator feed water were identified as the main organic component. It is shown that ion exchange is an efficient technology for removing organic impurities from makeup water for the heat-recovery steam generator.

Simultaneous detection and quantitation of organic impurities in methamphetamine by ultra-high-performance liquid chromatography-tandem mass spectrometry, a complementary technique for methamphetamine profiling.

The analysis of organic impurities plays an important role in the impurity profiling of methamphetamine, which in turn provides valuable information about methamphetamine manufacturing, in particular its synthetic route, chemicals, and precursors used. Ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) is ideally suited for this purpose due to its excellent sensitivity, selectivity, and wide linear range in multiple reaction monitoring (MRM) mode. In this study, a dilute-and-shoot UHPLC-MS/MS method was developed for the simultaneous identification and quantitation of 23 organic manufacturing impurities in illicit methamphetamine. The developed method was validated in terms of stability, limit of detection (LOD), lower limit of quantification (LLOQ), accuracy, and precision. More than 100 illicitly prepared methamphetamine samples were analyzed. Due to its ability to detect ephedrine/pseudoephedrine and its high sensitivity for critical target markers (eg, chloro-pseudoephedrine, N-cyclohexylamphetamine, and compounds B and P), more impurities and precursor/pre-precursors were identified and quantified versus the current procedure by gas chromatography-mass spectrometry (GC-MS). Consequently, more samples could be classified by their synthetic routes. However, the UHPLC-MS/MS method has difficulty in detecting neutral and untargeted emerging manufacturing impurities and can therefore only serve as a complement to the current method. Despite this deficiency, the quantitative information acquired by the presented UHPLC-MS/MS methodology increased the sample discrimination power, thereby enhancing the capacity of methamphetamine profiling program (MPP) to conduct sample-sample comparisons.

Qualitative and Quantitative Analysis of Organic Impurities in Feedwater of a Heat-Recovery Steam Generator

In recent years, combined-cycle units with heat-recovery steam generators have been constructed and commissioned extensively in the European part of Russia. By the example of the Kazan Cogeneration Power Station no. 3 (TETs-3), an affiliate of JSC TGK-16, the specific problems for most power stations with combined-cycle power units that stem from an elevated content of organic impurities in the feedwater of the heat-recovery steam generator (HRSG) are examined. The HRSG is fed with highly demineralized water in which the content of organic carbon is also standardized. It is assumed that the demineralized water coming from the chemical water treatment department of TETs-3 will be used. Natural water from the Volga River is treated to produce demineralized water. The results of a preliminary analysis of the feedwater demonstrate that certain quality indices, principally, the total organic carbon, are above the standard values. Hence, a comprehensive investigation of the feedwater for organic impurities was performed, which included determination of their structure using IR and UV spectroscopy techniques, potentiometric measurements, and element analysis; determination of physical and chemical properties of organic impurities; and prediction of their behavior in the HRSG. The estimation of the total organic carbon revealed that it exceeded the standard values in all sources of water comprising the feedwater for the HRSG. The extracted impurities were humic substances, namely, a mixture of humic and fulvic acids in a 20 : 80 ratio, respectively. In addition, an analysis was performed of water samples taken at all intermediate stages of water treatment to study the behavior of organic substances in different water treatment processes. An analysis of removal of the humus substances in sections of the water treatment plant yielded the concentration of organic substances on the HRSG condensate. This was from 100 to 150 μg/dm3. Organic impurities in boiler water can induce internal corrosion and deposits containing products of their degradation.

Point-of-Use Sampling and Organic Impurity Analysis for Bulk Gases in Semiconductor Processing

Highly purified gases, such as nitrogen, hydrogen and oxygen, are critical bulk gases in many semiconductor fabrication processes. The ongoing challenge in delivering such gases to the point-of-use is to prevent contamination of the gases by accumulation of organic impurities from tubing and components. This paper describes a point-of-use (POU) sampling and off-line analytical method for qualification and semi-quantification of trace organic impurities in CO2 gas as a model case. The sampling method is based upon a Tenax-GC adsorbent tube for sampling in gaseous CO2. Analysis of organic impurities trapped in the tube is achieved by thermal desorption gas chromatography mass-spectrometry (TD-GC/MS). From on-site sampling with a Tenax-GC adsorbent tube, we found that some hydrocarbons and halogenated carbons were detected from various point-of-uses and could define the contamination sources in CO2 delivery system.

Recent Advances in the Analysis of Organic Impurities of Active Pharmaceutical Ingredients and Formulations: A Review

Impurity profiling of active pharmaceutical ingredients is a critical quality control parameter during all stages of the development, production and stability testing of pharmaceutical formulations. Literature on this is continuously increasing, it is therefore important to keep track on the latest achievements and applications. This review presents an overview of the most recently published results on the analysis of organic impurities in pharmaceutical samples and active ingredients. Special attention is given to the most widely used techniques, such as liquid chromatography, capillary electrophoresis and mass spectrometry. Keywords: Impurity profiling, Analytical techniques, Stability-indicating assays, Active pharmaceutical ingredients, betamethasone-E-enolaldehyde, betamethasone-Z-enolaldehyde, Charged Aerosol Detector, CAD, mildronate, hydrophilic interaction chromatography, HILIC, Capillary electrophoresis, CE, cyclodextrin derivatives, Normal Stacking Mode, NSM, Reverse Migrating Micelles Mode, SRMM, APCI, Atmospheric Pressure Chemical Ionization, Atmospheric Pressure Ionization, Background Electrole, Charge Aerosol Detector, Micellar Electrokinetic Chromatography, Pseudostationary Phase, Thermal Surface Ionization

Drug intelligence based on MDMA tablets data: 2. Physical characteristics profiling

One of the tasks of the European project entitled “Collaborative Harmonisation of Methods for Profiling of Amphetamine Type Stimulants” (CHAMP) funded by the sixth framework programme of the European Commission was to develop a harmonised methodology for MDMA profiling and the creation of a common database in a drug intelligence perspective. Part I was dedicated to the analysis of organic impurities formed during synthesis in order to investigate traffic tendencies and highlight potential links between samples, whereas this part focuses on physical characteristics of the MDMA tablets. Diameter, thickness, weight and score were demonstrated to be reliable and relevant features in this drug intelligence perspective. Distributions of samples coming from the same post-tabletting batch (post-TB) and samples coming from different post-TB were very well discriminated by using the squared Euclidean or the Manhattan distance on standardised data. Our findings demonstrated the possibility to discriminate between MDMA samples issued from different post-TB and to find out links between samples coming from a same post-TB. Furthermore, the hypothesis that most of the MDMA samples found on the international market come from the same countries was supported.

Drug intelligence based on organic impurities in illicit MA samples

One major objective of the European project “Collaborative Harmonisation of Methods for Profiling of Amphetamine Type Stimulants” (CHAMP), funded by the sixth framework programme of the European Commission, consisted of the harmonisation of a gas chromatography/mass spectrometry (GC/MS) method for the analysis of organic impurities found in illicit methamphetamine (MA) samples in a drug intelligence perspective. Statistical analysis provided a selection of pertinent variables among the 43 organic impurities identified in the chromatograms. As for the 3,4-MethyleneDioxyMethAmphetamine (MDMA) study [1], correlation coefficients were used as a discrimination tool between populations of linked samples (from the same seizure) and unlinked samples (from different seizures). It was also shown that correlation measurements based on Pearson and cosine functions applied to the data pre-treated by normalisation to the sum of peak responses followed by the square root provided excellent discrimination between the two populations. The organic impurities profiling method was proved to be relevant for the characterization of samples from different seizures and their synthesis route patterns.

ToF‐SIMS analysis of organic impurities in UPW

AbstractWe have investigated adsorption of organic impurities in ultrapure water (UPW) on hydrophilic silicon wafer surface. The primary and tertiary amine molecules used as model compounds of organic impurities were adsorbed on the clean wafer surface during soaking in UPW. It was found that adsorbed quantities of relatively large tertiary amines among water‐soluble amines, such as (C3H7)3N and (C4H9)3N, were higher at relatively short soak time (two h in this experiment) than at longer one (24 h). Time‐of‐flight secondary‐ion mass spectrometry (ToF‐SIMS) is a very powerful tool for identification of trace organic contamination on wafer surface after UPW rinse from the studies of adsorption of the molecules present in UPW. Copyright © 2006 John Wiley & Sons, Ltd.

Growth and basic dielectric data of high quality TSCC crystals

AbstractTris‐sarcosine calcium chloride (TSCC) single crystals were grown from water solutions by the isothermal evaporation method. The growth solutions contained sarcosine and CaCl2 either in stoichiometric or nonstoichiometric ratio. The required phase diagram sarcosine–CaCl2H2O at 40 °C was determined by the synthetic method. PFT 400 MHz NMR was used for the analysis of organic impurities in sarcosine and TSCC. The crystals grown from both types of solutions had maximum values of the dielectric permittivity 10 to 200 times larger than those measured by other authors at comparable measuring frequencies and fields. It is discussed in terms of crystal quality.

Book Review: Die Analyse der organischen Verunreinigungen in Trink‐Brauch‐ und Abwässern [The Analysis of Organic Impurities in Drinking Water, Water for Industrial Use, and Effluents]. By W Leithe

Angewandte Chemie International Edition in EnglishVolume 13, Issue 5 p. 355-355 Book Review Book Review: Die Analyse der organischen Verunreinigungen in Trink-Brauch- und Abwässern [The Analysis of Organic Impurities in Drinking Water, Water for Industrial Use, and Effluents]. By W Leithe Dieter Eichelsdörfer, Dieter EichelsdörferSearch for more papers by this author Dieter Eichelsdörfer, Dieter EichelsdörferSearch for more papers by this author First published: May 1974 https://doi.org/10.1002/anie.197403551AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume13, Issue5May 1974Pages 355-355 RelatedInformation