Application of gas chromatography analysis to quality control of residual organic solvents in clopidogrel bisulphate

A direct-injection, split-mode capillary gas chromatographic procedure with a flame ionization detection is developed for the analysis of eight solvents used in the synthesis and purification of an anti-thrombotic drug clopidogrel bisulphate. The solvents analyzed were methanol, acetone, dichloromethane (DCM), 2-butanol, cyclohexane, toluene, acetic acid and N, N-dimethyl formamide (DMF). In addition, as a result of dehydration of 2-butanol during drying process, in clopidogrel bisulphate samples, significant amounts of 2-butanol dehydration products (1-butene, cis and trans isomers of 2-butene, 2,2'-oxydibutane and 1-(1-methylpropoxy)butane) may be detected. The content of each of these volatile products can be evaluated using the same gas-chromatographic method, with quantification based on the response factor established for the chromatographic peak of 2-butanol. For each solvent used in the process of clopidogrel bisulphate preparation, the procedure is validated for selectivity, linearity, recovery, precision, robustness, quantitation limit, and detection limit. All eight solvents plus five 2-butanol degradation products are fully separated. System suitability test is validated, and requirements are set. Based on a large number of result sets, retrospectively, from many different batches analyzed, conclusions were made about process variations and reliability and a lack of consistency was identified in the quality of the active substance from a particular producer source. Multivariate analysis was used as statistical technique to classify samples. From the analyzed set of 11 solvents, 6 of them were preselected based upon their occurrence in the samples and both Principal Component Analysis (PCA) and Hierarchical Cluster Analysis (HCA) were performed.

Download Full-text

Counterfeit medicines: a pilot study for chemical profiling employing a different proposal of an usual technique

Drug Analytical Research ◽

10.22456/2527-2616.107986 ◽

2020 ◽

Vol 4 (2) ◽

pp. 19-23

Author(s):

Maíra Santos ◽

Alessandro Kahmann ◽

Luiza Manica Caffarate ◽

Laura Ribas Ucha ◽

Renata Pereira Limberger ◽

...

Keyword(s):

Extraction Procedure ◽

Principal Component ◽

Standard Technique ◽

Hierarchical Cluster ◽

Pilot Project ◽

Chemical Profiling ◽

Counterfeit Medicines ◽

Flame Ionization ◽

Single Method ◽

Solid Form

Gas chromatography (GC) is a gold standard technique used in forensic laboratories, including for the characterization of counterfeit medicines. When coupled simultaneously to flame ionization (FID) and mass detector (MS) allow the identification and quantification of medicines and drugs employing a single method, besides permitting the application of chemometric tools for forensic intelligence purposes. Here is presented a pilot project that developed and applied a qualitative method for the analysis of counterfeit medicines comprised by amphetamine-type stimulants and antidepressants, through a simple extraction procedure followed by GC-FID/MS analysis, with application of exploratory tools by Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA). The main purpose was to identify similarities between the all compounds detected in the irregular medicines allowing the traceability of illicit producers with the creation of a common data base. Through the analyses it was verified that different producers of counterfeit medicines labeled as Sibutramine, added a mixture of Caffeine and Benzocaine in their formulation, respecting the same ratio of 2.2:1. HCA was able to confirm these results, showing the presence of both falsifications in the same cluster, representing the best tool to identify similar characteristics among the samples – when compared to PCA. Other interesting finding was the use of Fluoxetine as a falsification of counterfeit medicines labeled as Sibutramine and Diethylpropion. Another seized sample labeled as “Nobesio Forte”, marketed as a mix of stimulants, showed only Caffeine and Lidocaine in its formulation. The pilot project applied primarily to 45 samples of counterfeit medicines containing amphetamine-type stimulants and antidepressants, showed the capability of perform the chemical profiling of counterfeit medicines in the solid form - powder, capsules and tablets. Further analysis can be performed for different types of medicines in solid form using the developed method, allowing the construction of a single database to perform the chemical profiling of counterfeit medicines, enabling the traceability of illicit producers.

Download Full-text

Identification of the Organic Volatile Impurities in Ezitamibe using GC-HS Technique

Asian Journal of Chemistry ◽

10.14233/ajchem.2021.23071 ◽

2021 ◽

Vol 33 (3) ◽

pp. 605-610

Author(s):

Durgababu Rapeti ◽

Kapavarapu Maruthi Venkata Narayanarao ◽

Pulipaka Shyamala ◽

Rallabhandi Murali Krishna

Keyword(s):

Chromatographic Method ◽

Isopropyl Alcohol ◽

Organic Chemical ◽

Dimethyl Formamide ◽

Flame Ionization ◽

Drug Substances ◽

Periodic Analysis ◽

Ionization Mode ◽

Gas Chromatographic Method ◽

Volatile Impurities

Ezetimibe prevents intestinal cholesterol synthesis, which in turn reduces the quantity of cholesterol and thereby helps to reduce heart problems and strokes. In the production of ezetimibe, several organic chemical solvents such as methanol, acetone, isopropyl alcohol, dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, toluene and dimethyl formamide were used. The measurement of residual solvents is necessary for release checks of all drug substances, based on sound manufacturing processes. The analysis of above mentioned nine solvents in ezetimibe drug was investigated using gas chromatographic method employing detection with flame ionization mode. All analyses were performed using ZB-624 column (30 m length × 0.53 mm identification, 3.0 μm thickness film). The column oven temperature flux was managed to maintain for 11 min at 40 ºC and then continued to upsurge to a temperature close of 240 ºC at a rate of 20 ºC/min and retained for 4 min. The flame ionization detector and injector port were managed at 260 and 200 ºC, respectively. Results after the validation of the gas chromatographic method showed the satisfactory linearity, sensitivity, robustness, accuracy, selectivity and precision for the tested organic solvents. This gas chromatographic approach can therefore be exploited in the assessment of studied nine residual chemical solvents for periodic analysis by gas chromatography for samples of ezetimibe drug.

Download Full-text

Chemical Profile and Chemometric Analysis of Genetically Modified Soybeans Produced in the Triângulo Mineiro Region (MG), Brazil

Journal of Agricultural Studies ◽

10.5296/jas.v9i2.18139 ◽

2021 ◽

Vol 9 (2) ◽

pp. 73

Author(s):

Marco Aurélio Borba Moreira ◽

Amilton Diniz Souza ◽

Fernanda Barbosa Borges Jardim ◽

Luís Carlos Scalon Cunha ◽

Mário Machado Martins ◽

...

Keyword(s):

Chemical Composition ◽

Genetically Modified ◽

Direct Injection ◽

Principal Component ◽

Hierarchical Cluster ◽

Ionization Mass ◽

Genetic Characteristics ◽

Positive Mode ◽

Soy Production ◽

The City

Soy production in Brazil is an important factor for the agro-industrial, economic, and social development of the country. The expansion of soy in the Brazilian territory is mainly due to the incorporation of new genetic characteristics into cultivars that granted resistance to the Cerrado conditions and to herbicides. Currently, Brazilian soy production is the result of genetically modified cultivars. Studies regarding the chemical composition of soybeans show that qualitative and quantitative variations can occur, depending on the region of production. This work aimed to investigate the chemical composition of soybeans produced in different cities of the Triângulo Mineiro region/MG, Brazil (Harvest 2017/2018) and stored in three warehouses located in the city of Uberaba/MG. The grain analysis was made by liquid chromatography coupled to electrospray ionization mass spectrometry (LC-MS-ESI). The classes of metabolites identified from methanolic extraction were organic acids, phenolic compounds, flavonoids, sugars, amino acids, dipeptides, nitrogenous bases, nucleosides, sphingolipids, and fatty acids. The isoflavones genistein, daidzein, glycitein, genistin, acetyldaidzin, and acetylgenistin were identified in soybeans from the three warehouses. The flavonoid eriodictyol-O-hexoside was also found. The Principal Component Analysis (PCA) from the mass spectrum data obtained by direct injection in the negative and positive modes evidenced the well-defined separation of three groups, indicating that there was variance among the soy samples from each warehouse. The samples from warehouses 1 and 3 showed greater similarity in the Hierarchical Cluster Analysis (HCA) in negative mode, while in positive mode, the samples from warehouses 2 and 3 presented greater similarity.

Download Full-text

PEMODELAN STATISTICAL DOWNSCALING DENGAN PEUBAH DUMMY BERDASARKAN TEKNIK CLUSTER HIERARKI DAN NON- HIERARKI UNTUK PENDUGAAN CURAH HUJAN

Indonesian Journal of Statistics and Its Applications ◽

10.29244/ijsa.v3i3.471 ◽

2019 ◽

Vol 3 (3) ◽

pp. 295-309

Author(s):

Sitti Sahriman ◽

Anisa Kalondeng ◽

Vieri Koerniawan

Keyword(s):

Statistical Downscaling ◽

Principal Component Regression ◽

Circulation Model ◽

Principal Component ◽

Hierarchical Cluster ◽

Statistical Technique ◽

Rainfall Data ◽

Global Circulation Model ◽

Cluster Technique ◽

Dummy Variables

Statistical downscaling (SD) is a statistical technique used to predict local scale rainfall based on global atmospheric circulation. The global scale climate variable used is precipitation from GCM (Global Circulation Model). However, the precipitation data of GCM outputs have a large dimension, giving rise to multicollinearity in the data. This problem is handled by the Principal Component Regression (PCR) method. In addition, the SD models have heterogeneous error variances. The dummy variable is added to the PCR models to solve the problem. Hierarchical (k-means) and non-hierarchical cluster techniques (average linkage, median linkage, and ward linkage) are used in modeling to determine rainfall data groups. Furthermore, the group formed is the basis of the formation of dummy variables. This study aims to estimate local rainfall data in Pangkep district as a salt-producing area in South Sulawesi. There are 4 dummy variables based on the 5 groups formed. Dummy variables are able to improve predictions from the PCR models. R2 values of the PCR-dummy models (ranging from 89.89% to 95.58%) are relatively higher than the PCR models (ranging from 55.87% to 57.61%). This result is also consistent with the model validation stage. The PCR-dummy models based on non-hierarchical cluster techniques (k-means) are better than the PCR-dummy models based on cluster hierarchy techniques. In general, the best model is the PCR-dummy model of the non-hierarchical cluster technique (k-means ) and involves 4 main components.

Download Full-text

Seasonal variability of the essential oil of Hesperozygis ringens (Benth.) Epling.

Brazilian Journal of Biology ◽

10.1590/1519-6984.16314 ◽

2016 ◽

Vol 76 (1) ◽

pp. 176-184 ◽

Cited By ~ 11

Author(s):

C. G. Pinheiro ◽

C. M. Machado ◽

L. P. Amaral ◽

D. T. Silva ◽

C. A. A. Almeida ◽

...

Keyword(s):

Gas Chromatography ◽

Chemical Composition ◽

Essential Oil ◽

Native Species ◽

Chemical Constituents ◽

Principal Component ◽

Hierarchical Cluster ◽

Flame Ionization ◽

Four Seasons ◽

Three Samples

Abstract This study was developed to evaluate the effect of seasonality on the yield and chemical composition of the essential oil (EO) of Hesperozygis ringens (Benth.) Epling, a native species from the Brazilian Pampa. Leaves were collected from four specimens of a single population in each of the four seasons for a year and were extracted in triplicate by hydro-distillation for 2 hours. The yield of EO (% w/w) was calculated on fresh weight basis (FWB), and the 16 oil samples were analyzed by gas chromatography coupled to mass spectrometry (GC-MS) and gas chromatography with flame ionization detector (GC-FID). Hierarchical Cluster Analysis (HCA) and Principal Component Analysis (PCA) were used as statistical tools to evaluate differences in chemical composition. The highest yields were obtained in autumn, spring and summer (2.32-4.38%), while the lowest yields were detected in winter, ranging from 1.15 to 1.91%. Oxygenated monoterpenoids were the predominant class of chemical constituents in the EO obtained in all seasons, showing the highest contents in autumn and summer, and pulegone was identified as a major compound, whose contents varied between 54.13 and 81.17%. The EO samples were divided into three chemical groups by HCA and PCA and were assigned to the same group, except for the three samples gathered in winter. The results showed a seasonal influence on the yield and chemical composition of the EO.

Download Full-text

Assessment of diurnal variation in Ocimum sanctum Linn. by gas chromatographic fingerprint analysis coupled with chemometric methods

Plant Science Today ◽

10.14719/pst.2018.5.3.413 ◽

2018 ◽

Vol 5 (3) ◽

pp. 131-134 ◽

Cited By ~ 1

Author(s):

Nikunj Patel ◽

Niranjan Kanaki ◽

Vinit Movaliya

Keyword(s):

Chemical Composition ◽

Diurnal Variation ◽

Principal Component ◽

Hierarchical Cluster ◽

Ocimum Sanctum ◽

Chemical Compositions ◽

Chemometric Methods ◽

Flame Ionization ◽

Ocimum Species ◽

Significant Difference

Vast intra-specific variations, especially diurnal, geographical and seasonal, have been reported in the chemical composition of essential oils of Ocimum species. The study was conducted to assess diurnal variation in the chemical composition of the leaves of Ocimum sanctum. The leaf samples collected at different times of the day were analyzed by gas chromatography coupled with flame ionization detector (GC-FID). The chromatographic fingerprints of different leaf samples were analyzed by chemometric methods like principal component analysis and hierarchical cluster analysis. No significant difference was found in the chemical compositions of the leaf samples collected at different times of the day. The results lead to a conclusion that O. sanctum does not exhibit diurnal variation in its chemical composition, unlike O. gratissimum.

Download Full-text

Quality evaluation of tugaksheeree samples by ATR-FTIR spectroscopy using multicomponent analysis

The Natural Products Journal ◽

10.2174/2210315510999200408125555 ◽

2020 ◽

Vol 10 ◽

Cited By ~ 1

Author(s):

Nikunj D. Patel ◽

Niranjan S. Kanaki

Keyword(s):

Principal Component Analysis ◽

Cluster Analysis ◽

Quality Evaluation ◽

Principal Component ◽

Hierarchical Cluster ◽

Attenuated Total Reflectance ◽

Chemometric Methods ◽

Total Reflectance ◽

Fingerprint Region ◽

Ftir Technique

Background: Numerous Ayurvedic formulations contains tugaksheeree as key ingredient. Tugaksheereeis the starch gained from the rhizomes of two plants, Curcuma angustifoliaRoxb. (Zingiberaceae) and Marantaarundinacea (MA) Linn. (Marantaceae). Objective: The primary concerns in quality assessment of Tugaksheeree occur due to adulteration or substitution. Method: In current study, Fourier transform infrared (FTIR) technique with attenuated total reflectance (ATR) facility was used to evaluate tugaksheeree samples. Total 10 different samples were studied and transmittance mode was kept to record the spectra devoid of pellets of KBR. Further treatment was given with multi component tools by considering fingerprint region of the spectra. Multivariate analysis was performed by various chemometric methods. Result: Multi component methods like Principal Component Analysis (PCA), and Hierarchical Cluster Analysis (HCA)were used to discriminate the tugaksheeree samples using Minitab software. Conclusion: This method can be used as a tool to differentiate samples of tugaksheeree from its adulterants and substitutes.

Download Full-text

Multivariate Statistical Approach for Nephrines in Women with Obesity

Molecules ◽

10.3390/molecules26051393 ◽

2021 ◽

Vol 26 (5) ◽

pp. 1393

Author(s):

Ralitsa Robeva ◽

Miroslava Nedyalkova ◽

Georgi Kirilov ◽

Atanaska Elenkova ◽

Sabina Zacharieva ◽

...

Keyword(s):

Type 2 Diabetes ◽

Metabolic Syndrome ◽

Data Analysis ◽

Stress Response ◽

Exploratory Data Analysis ◽

Principal Component ◽

Hierarchical Cluster ◽

Obese Women ◽

Exploratory Data

Catecholamines are physiological regulators of carbohydrate and lipid metabolism during stress, but their chronic influence on metabolic changes in obese patients is still not clarified. The present study aimed to establish the associations between the catecholamine metabolites and metabolic syndrome (MS) components in obese women as well as to reveal the possible hidden subgroups of patients through hierarchical cluster analysis and principal component analysis. The 24-h urine excretion of metanephrine and normetanephrine was investigated in 150 obese women (54 non diabetic without MS, 70 non-diabetic with MS and 26 with type 2 diabetes). The interrelations between carbohydrate disturbances, metabolic syndrome components and stress response hormones were studied. Exploratory data analysis was used to determine different patterns of similarities among the patients. Normetanephrine concentrations were significantly increased in postmenopausal patients and in women with morbid obesity, type 2 diabetes, and hypertension but not with prediabetes. Both metanephrine and normetanephrine levels were positively associated with glucose concentrations one hour after glucose load irrespectively of the insulin levels. The exploratory data analysis showed different risk subgroups among the investigated obese women. The development of predictive tools that include not only traditional metabolic risk factors, but also markers of stress response systems might help for specific risk estimation in obesity patients.

Download Full-text

Spectroscopy as a useful tool for the identification of changes with time in post-mortem vitreous humor for forensic toxicology purposes

Monatshefte für Chemie - Chemical Monthly ◽

10.1007/s00706-021-02786-8 ◽

2021 ◽

Author(s):

Anna Wójtowicz ◽

Agata Mitura ◽

Renata Wietecha-Posłuszny ◽

Rafał Kurczab ◽

Marcin Zawadzki

Keyword(s):

Ir Spectra ◽

Forensic Toxicology ◽

Principal Component ◽

Hierarchical Cluster ◽

Vitreous Humor ◽

Attenuated Total Reflection ◽

Glass Slides ◽

Added Benefit ◽

Ft Ir ◽

Non Destructive

AbstractVitreous humor (VH) is an alternative biological matrix with a great advantage of longer availability for analysis due to the lack of many enzymes. The use of VH in forensic toxicology may have an added benefit, however, this application requires rapid, simple, non-destructive, and relatively portable analytical analysis methods. These requirements may be met by Fourier transform infrared spectroscopy technique (FT-IR) equipped with attenuated total reflection accessory (ATR). FT-IR spectra of vitreous humor samples, deposited on glass slides, were collected and subsequent chemometric data analysis by means of Hierarchical Cluster Analysis and Principal Component Analysis was conducted. Differences between animal and human VH samples and human VH samples stored for diverse periods of time were detected. A kinetic study of changes in the VH composition up to 2 weeks showed the distinction of FT-IR spectra collected on the 1st and 14th day of storage. In addition, data obtained for the most recent human vitreous humor samples—collected 3 and 2 years before the study, presented successful discrimination of all time points studied. The method introduced was unable to detect mephedrone addition to VH in the concentration of 10 µg/cm3. Graphic abstract

Download Full-text

Ayurvedic formulations containing benzoic and ascorbic acids as additives: benzene formation during storage and impact of additives on quality parameters

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2020-0012 ◽

2020 ◽

Vol 0 (0) ◽

Author(s):

Priyanka Sharma ◽

Mukesh Maithani ◽

Vikas Gupta ◽

Parveen Bansal

Keyword(s):

Ascorbic Acid ◽

Quality Parameters ◽

Over The Counter ◽

Flame Ionization ◽

Class 1 ◽

Short And Long Term ◽

Pharmaceutical Industries ◽

Increasing Demand ◽

Gas Chromatographic Method ◽

Ascorbic Acids

AbstractObjectivesAyurvedic formulations are becoming the prior choice of people as health care supplements. The increasing demand for these formulations has led to extensive development of Ayurvedic pharmaceutical industries worldwide. The reaction between the preservatives (sodium benzoates and ascorbic acid) used in these formulations could generate benzene. Benzene is classified as class-1 human carcinogen and responsible for various short and long term health effects.MethodsIn this study, 25 formulations (containing ascorbic acid and sodium benzoate) of various manufacturers available as over the counter products were obtained and their benzene content were determined using gas chromatograph with flame ionization detector.ResultsThe result showed that 64% of the formulations were free from benzene contamination whereas 36% of formulations were found to be contaminated with benzene. A simple, less time-consuming, economic, and validated gas chromatographic method for estimation of benzene in Ayurvedic formulations was also developed successfully in present study.ConclusionsThe data revealed that the level of benzene was within permissible limits, yet the presence of a carcinogen in the marketed formulations intended for internal use is an alarming situation.

Download Full-text