Gas Chromatographic Method for Identification and Quantification of Commonly Used Residual Solvents in Pharmaceuticals Products

Background: Impurities are not expected in the final pharmaceutical products. All impurities should be regulated in both drug substances and drug products in accordance with pharmacopeias and ICH guidelines. Three different types of impurities are generally available in the pharmaceutical’s product specification: organic impurities, inorganic impurities, and residual solvents. Residual solvents are organic volatile chemicals used or generated during the manufacturing of drug substances or drug products. Purpose: The aim of this study is to develop a cost-effective gas chromatographic method for the identification and quantification of some commonly used solvents—methanol, acetone, isopropyl alcohol (IPA), methylene chloride, ethyl acetate, tetrahydrofuran (THF), benzene, toluene, and pyridine—in pharmaceutical product manufacturing. This method will be able to identify and quantify the multiple solvents within a single gas chromatographic procedure. Method: A gas chromatography (GC) equipped with a headspace sampler and a flame ionization detector, and a column DB 624, 30-meter-long × 0.32-millimeter internal diameter, 1,8 μm-thick, Brand-Agilent was used to develop this method. The initial GC oven temperature was 40°C and held for 5 minutes. It was then increase to 80˚C at a rate of 2˚C per minute, followed by a further increase to 225˚C at a rate of 30˚C per minute, with a final hold at 225˚C for 10 minutes. Nitrogen was used as a carrier gas at a flow rate of 1.20 mL per minute. Dimethyl sulfoxide (DMSO) was selected as sample solvent. Results: The developed method is precise and specific. The percent RSD for the areas of six replicate injections of this gas chromatographic method was within 10.0 and the recovery result found within 80.0% to 120.0%.

Determination of 14 Organophosphorus Pesticide Residues in Mutton by Gel Permeation Chromatography-Gas Chromatography-Mass Spectrometry(GPC-GC-MS)

[Objectives]This study was conducted to purify mutton samples by gel permeation chromatography(GPC).[Methods]Fourteen organophosphorus pesticide residues in samples were qualitatively and quantitatively analyzed by gas chromatography-mass spectrometry(GC-MS)in selective ion scanning mode(SIM).[Results]The organophosphorus pesticide standard solutions showed good linearity in the mass concentration range of 0.1-10.0μg/ml with correlation coefficients(r)not lower than 0.999,and the detection limits(S=3 N)ranged from 0.01 to 0.05 mg/kg.The average recovery values were in the range of 80.2%-99.7%,with relative standard deviations(RSDs,n=3)in the range of 1.8%-6.3%,at the addition levels of 0.5,1.0 and 2.0 mg/kg.[Conclusions]The method is simple,sensitive and accurate,and can be used for the determination of organophosphorus pesticide residues in mutton.

Evaluation of reservoir connectivity using whole-oil gas chromatographic fingerprint technology: A case study from the Es_3~3 reservoir in the Nanpu Sag, China

In this study, whole-oil gas chromatographic fingerprint analyses were performed on oils from the Es3^3 reservoir in the Liubei area of the Nanpu Sag. The gas chromatographic peaks of cyclic and branched alkanes with relatively high resolution from nCl0 to nC25 were selected to establish a database of whole-oil gas chromatographic peak height ratio fingerprints. Reservoir fluid connectivity was identified by using clustering analysis. This method can reflect the gas chromatography fingerprint information accurately and entirely, and avoid the one-sidedness of the star diagram method which only selects several fixed gas chromatographic peaks.

Volatile Compounds Fingerprints for White Duck down and White Goose down Determined by Gas Chromatography-Ion Mobility Spectrometry

This work first describes a simple approach for the untargeted profiling of volatile compounds for distinguishing between white duck down (WDD) and white goose down (WGD) based on resolution-optimized GC-IMS combined with optimized chemometric techniques, namely PCA. The detection method for down samples was established by using GC-IMS. Meanwhile, the reason of unpleasant odors caused by WDD was explained on the basis of the characteristic volatile compounds identification. GC-IMS fingerprinting can be considered a revolutionary approach for a truly fully automatable, cost-efficient, and in particular highly sensitive method. A total of 22 compounds were successfully separated and identified through GC-IMS method, and the significant differences in volatile compounds were observed in three parts of WDD and WGD samples. The most characteristic volatile compounds of WGD belong to aldehydes, whereas carboxylic acids from WDD were detected generated by autoxidation reaction. Meanwhile, the main reason of unpleasant odor generation was possibly attributed to the high concentration of volatile carboxylic acids of WDD. Therefore, the constructed model presents a simple and efficient method of analysis and serves as a basis for down processing and quality control.

Study on the Chromatographic Fingerprint of Volatile Constituents from Acacia Honey

[Objective] The experiment aimed to study chromatographic fingerprint in volatile components of acacia honey and provide scientific evaluation and effective control on quality of acacia honey.[Method] Using solid-phase microextraction method to separate and detect volatile components and construct chromatographic fingerprint.[Result] The honey was preheated for 15 min in water bath at 40 ℃ and solid-phase microextraction 85 μmPA was used to extract in overhead air about 30 min,then put it into the injector and desorpted 3 min,which is in 230 ℃.The Supelco WaxTM10 30 m×0.25 mm×0.25 μm column and gradient heating program was the best method to separate volatile components from honey.83 fingerprint peaks were constructed,among which 17 common fingerprint peaks were comprised of chromatographic fingerprint of volatile components of acacia honey.[Conclusion] The chromatographic fingerprint could provide reference for quality control of acacia honey.

Classification of Chinese Traditional Drug-"Beimu" (Bulbus Fritillariae) by Pyrolysis High Resolution Gas Chromatography-Pattern Recognition

The combination of pyrolysis high resolution gas chromatography and pat- tern recognition techniques is a powerful tool for the classification of traditional Chinese drug.A study has been completed on 55 Beimu samples of five different geographic origins: Eastern China.Central China.South-western China,North-western China and North-eastern China.Principal component analysis and SIMCA are applied to effectively classifying the samples according to the origin of the plants.The chemical information contained in the high resolution gas chromatographic data is sufficient to characterize the geographic origin of sam- pies.

Determination of phthalate esters in fat-containing foods by packed nanofiber solid-phase extraction column and gas chromatography

A new method for simultaneous determination of four phthalate esters （ PAEs） in commercial fat-containing foods was developed by the combination of a packed nanofibers column based on solid-phase extraction with gas chromatography-flame ionization detector （ GC-FID ）. Conditions for obtaining optimum extraction efficiency such as extraction solvents, morphologies of adsorbent, ion strength and pH were investigated and optimized in detail. Under the optimized conditions, the limits of detection （LODs） found for dibutyl phthalate （DBP） , butyl benzyl phthalate （BBP）, diethyl hexyl phthalate （DEHP） and di-n-octyl phthalate （DNOP） were 50, 25, 50 and 25 ng/g, respectively. Good linearity of four PAEs was achieved in the range of 50 to 4 000 ng/g. The proposed method was applied for analyzing different kinds of fat-containing samples. PAEs in commercial fat-containing samples can be highly extracted by a packed solid-phase extraction column of 5 mg polystyrene （ PS） nanofibers. The satisfactory average recoveries were obtained in the range of 96. 7% to 102. 3% , and the relative standard deviations （RSDs） below 5% were achieved. The proposed method reduces the organic solvent consumption, the complex and tedious procedures for sample pretreatment, and achieves high sensitivity and reproducibility for the investigated PAEs.

Determination of Dichlofluanid Residue in Soybean by Capillary Collumns Gas Chromatography

A method for the determination of dichlofluanid residue by Capillary Collumns Gas Chromatography was established in this study.Samples were extracted with acetone and subjected to through liquid-liquid extraction with N-hexane,and then they were cleanup with column that filled with florisil,subsequently separated by Capillary Column Gas Chromatography,and the electron capture detector （ECD） was used for detection.The detection limit of this method was 0.005 mg/kg （S/N=3）,and this method was rapid,sensitive and accurate,and was applied in the determination of dichlofluanid residue in soybean.

Separation Properties of a New Polysiloxane-Anchored β-Cyclodextrin Derivative as Gas Chromatography Stationary Phase

A new capillary gas chromatography stationary phase, monokis (2,6 di O benzyl 3 O propyl (3’)) hexakis(2,6 di O benzyl 3 O methyl) β CD bonded polysiloxane, was synthesized. It exhibited separation abilities to disubstituted benzene isomers and some chiral solutes. It was also found that the polarity of CD derivatives can be lowered both by chemically bonding it to polysiloxane and by diluting it in polysiloxane. The separation abilities of the polysiloxane anchored CDs (SP CD) are higher than that of the unbonded CDs (S CD) and the diluted S CD at lower column temperature. Hydrosilylation reaction is one of the best methods to lower the operating temperature of CDs.

Pyrolysis-Gas Chromatography/Mass Spectrometry for Microstructure and Pyrolysis Pathway of Polyester-Polyether Multiblock Copolymer

The composition and sequence distribution of monomeric units in polyester polyether multiblock copolymer were studied by pyrolysis? gas chromatography (PGC) and pyrolysis gas chromatography/mass spectrometry (PGC/MS). PGC was applied to study the F t curve of the multiblock copolymer and PGC/MS was used to separate and identify the pyrolyzates. DTA experiment was used to study the decomposition temperature. The results show that the beginning point of elastomer’s decomposition was about 300?℃ and the decomposition temperature of most of the sample was 550?℃. Many pyrolyzates were produced because of the breaking of weak bonds in the sample. The possible microstructure was verified and the pyrolysis pathway of the copolymer was investigated.

Synthesis and Characterization of Peralkylated β-Cyclodextrins Used as Gas Chromatographic Stationary Phasest

Six peralkylated β- cyclodec\xtrins used as capillary gas chromatographic stationary phases were prepared and characterized by differential by differential scannning calorimetry(DSC) and pyrolysis gas chromatography (PyGC). The DSC profiles illustrated that the peralkylated β-cyclodextrins synthesized possess the supercoooled state and the glass state below their melting point The PYGC results showed that the long-chain alkylated β-cyclodextrins are more thermostable than the short-chain. one All ofthese peralkylated β-cyclodextrins are suitable for use as capillary column gas chromatographic stationary phases,which can easily be coatal on the fused silica capilary columns and have nice chromatographic retention behaviour. For example, the capillary colunns coated with these materials can excellently separate three methylphenol isomers and six dimehylphenol isomers.

Application of Pyrolysis-Gas Chromatography in Explosive and Propellant Analysis

Applications of pyrolysis-gas chromatography and pyrolysis capillary gas chromatography in explosive and propellant analysis are reviewed, including the identification of explosives and propel- lants, the investigation of the thermal decomposition of nitrocellulose (NC), cyclotetramethylene tetranitramine (HMX)and cyclotrimethylene trinitramine (RDX), and the study of the wear- reducing mechanism of polyurethane additive in propellant gain.

Enantioselective Determination of R-(-)-and S-(+)-Mexiletine in Microsomal Incubates by Capillary gas Chromatography

A method for the assay of R ( ) and S (+) mexiletine in rat liver microsomal incubates was developed. The method involved extraction of mexiletine from the microsomal incubates, and formation of mexiletine diastereomeric derivatives with a chiral reagent S ( ) N trifluoroacetyl prolyl chloride. Separation and quantitation of the diastereomeric mexiletine derivatives were carried out by a capillary gas chromatographic system with flame ionization detection. The assay was linear from 5 to 500 μg/ml for each enantiomer. The average recoveries of analytical method were 93 31±5 59% and 93 10±5 11% for R ( ) and S (+) mexiletine, respectively. The limits of detection and quantitation for the method were 1 0 μg/ml and 5 0 μg/ml for the R ( ) and S (+) mexiletine isomers, respectively. The reproducibility in the assay was better than 16.5% (RSD). The method has been applied to the metabolism study of R ( ) and S (+) mexiletine in rat liver microsomal incubates.

Development of the fingerprints for the quality evaluation of Viscum coloratum by high performance liquid chromatography

A high-performance liquid chromatography coupled ultraviolet （HPLC-UV） method was developed for a chemical fingerprint analysis of Viscum coloratura. Eighteen peaks were selected as the common peaks and Homoeriodictyol-7-O-β-D-apiosiyl-（1→2）-β-D-glucoside was used as a reference. The relative areas of common peaks were used for hierarchical clustering analysis and similarity calculation. Thirty-seven samples collected from different sources were classified into five groups. The similarities of 21 batches Viscum coloratura samples were beyond 0.90. The results obtained suggest that the chromatographic fingerprint can efficiently identify Viscum coloratum. Additionally, the fingerprints can then be used to evaluate the correlation between Viscum coloratura and hosts.

Cross-Linked Crown Ether-SE-54 as Stationary Phase for Open-Tubular Column Gas Chromatography

The cross-linking of crown ether-SE-54 in fused-silica capillary columns were initiated by dicumyl peroxide(DCUP),azo-bis-isobutyronitrile (AIBN)and ozone(O_3).Parameters of evaluation such as polarity,selectivity, phase transition temperature and thermal stability were studied and compared with those of poly(crown ether)stationary phase.

Metabolomics of gastric cancer metastasis detected by gas chromatography and mass spectrometry

AIM:To elucidate the underlying mechanisms of metastasis and to identify the metabolomic markers of gastric cancer metastasis.METHODS:Gastric tumors from metastatic and nonmetastatic groups were used in this study.Metabolites and different metabolic patterns were analyzed by gas chromatography,mass spectrometry and principal components analysis (PCA),respectively.Differentiation performance was validated by the area under the curve (AUC) of receiver operating characteristic curves.RESULTS:Twenty-nine metabolites were differentially expressed in animal models of human gastric cancer.Of the 29 metabolites,20 were up-regulated and 9 were down-regulated in metastasis group compared to non-metastasis group.PCA models from the metabolite profiles could differentiate the metastatic from the nonmetastatic specimens with an AUC value of 1.0.These metabolites were mainly involved in several metabolic pathways,including glycolysis (lactic acid,alaline),serine metabolism (serine,phosphoserine),proline metabolism (proline),glutamic acid metabolism,tricarboxylic acid cycle (succinate,malic acid),nucleotide metabolism (pyrimidine),fatty acid metabolism (docosanoic acid,and octadecanoic acid),and methylation(glycine).The serine and proline metabolisms were highlighted during the progression of metastasis.CONCLUSION:Proline and serine metabolisms play an important role in metastasis.The metabolic profiling of tumor tissue can provide new biomarkers for the treatment of gastric cancer metastasis.

Chromatographic fingerprinting and quantitative analysis for the quality evaluation of Xinkeshu tablet

A simple, sensitive and accurate method based on high performance liquid chromato- graphy （HPLC） with diode array detector （DAD） was developed and validated for systematic quality evaluation of one type of traditional Chinese medicine preparations named Xinkeshu （XKS） tablet. In this study, the chromatographic fingerprints of XKS tablet were developed first, 23 peaks were selected as the common peaks to evaluate the similarities among different batches of XKS samples, which were manufactured in a long time span of three years. Additionally, simultaneous quantification of six markers in XKS tablet, including Danshensu, Protocatechuic aldehyde, Puerarin, Daidzin, Salvianolic acid B and Daidzein, was performed. The validation results showed that the developed method was specific, accurate, precise and robust. The preliminary explanation on why a close similarity between fingerprints did not exactly mean similar contents of chemical components in samples was given. The contribution of each chromatographic peak to similarity was also evaluated. The developed method offers an efficient, reliable and practical approach for systematic quality evaluation of XKS tablet.

Gas chromatography/mass spectrometry based metabolomic study in a murine model of irritable bowel syndrome

AIM To study the role of microbial metabolites in the modulation of biochemical and physiological processes in irritable bowel syndrome(IBS).METHODS In the current study, using a metabolomic approach, we analyzed the key metabolites differentially excreted in the feces of control mice and mice with IBS, with or without Clostridium butyricum(C. butyricum) treatment. C57 BL/6 mice were divided into control, IBS, and IBS + C. butyricum groups. In the IBS and IBS + C. butyricum groups, the mice were subjected to water avoidance stress(WAS) for 1 h/d for ten days. Gas chromatography/mass spectrometry(GC-MS) together with multivariate analysis was employed to compare the fecal samples between groups. RESULTS WAS exposure established an appropriate model of IBS in mice, with symptoms of visceral hyperalgesia and diarrhea. The differences in the metabolite profiles between the control group and IBS group significantly changed with the progression of IBS(days 0, 5, 10, and 17). A total of 14 differentially excreted metabolites were identified between the control and IBS groups, and phenylethylamine was a major metabolite induced by stress. In addition, phenylalanine metabolism was found to be the most relevant metabolic pathway. Between the IBS group and IBS + C. butyricum group, 10 differentially excreted metabolites were identified. Among these, pantothenate and coenzyme A(Co A) biosynthesis metabolites, as well as steroid hormone biosynthesis metabolites were identified as significantly relevant metabolic pathways.CONCLUSION The metabolic profile of IBS mice is significantly altered compared to control mice. Supplementation with C. butyricum to IBS mice may provide a considerable benefit by modulating host metabolism.

Studies on Chromatography Fingerprint of Hongqi by High-performance Liquid Chromatography

Chromatography fingerprint (CFP) of 10 samples of hongqi were studied. 23 common peaks were analyzed, their average similarity was 97.29%. CFP were positioned with main index composition such as formononetin, calycosin and then the contents of index composition were determined. The character and exclusive of CFP of 10 samples of hongqi were clear. CFP and content determination of index composition of hongqi could be used to evaluate the quality of hongqi comprehensively.

Detection of Tocopherol in Oilseed Rape (Brassica napus L.) Using Gas Chromatography with Flame Ionization Detector

The variation among Chinese genotypes of Brassica napus L. for seed tocopherols content and their analysis using gas chromatography has not been comprehensively reported till to date. In the present study, the tocopherol contents of four Chinese genotypes of Brassica napus L., namely, Gaoyou 605, Zhejiang 619, Zheshuang 758, and Zheshuang 72, were evaluated using three modified sample preparation protocols （P1, P2, and P3） for tocopherol extraction. These methods were distinguished as follows. Protocol one （P1） included the evaporation of solvent after extraction without silylation. Protocol two （P2） followed the direct supernatant collection after overnight extraction without drying and silylation. Protocol three （P3） included trimethylsilylation with N,O-bis（trimethylsilyl） trifluoroacetamide. Genotypic comparison of tocopherol and its isoforms revealed that Gaoyou 605 was dominant over the other genotypes with （140.5＋ 10.5）, （316.2＋ 9.2）, and （559.1＋ 24.3） ~tg g-~ of seed meal ct-, 7-, and total （T-） tocopherol, respectively, and a 0.44＋0.04 ^- to 7-tocopherol ratio. The comparison of the sample preparation protocols, on the other hand, suggests that P3 is the most suitable method for the tocopherol extraction from Brassica oilseeds and for the analysis of tocopherols using gas chromatography flame ionization detector （GC-FID）. Trimethylsilylation is the key step differentiating P3 from P1 and P2. Variations detected in tocopherol contents among the Chinese rapeseed （B. napus） genotypes signify the need to quantify a wide range of rapeseed germplasm for seed tocopherol dynamics in short and crop improvement in long.