Method Development And Validation For Determination Of Residual Solvents In Racecadotril By Gas Chromatography

2020 ◽  
Vol 16 ◽  
Author(s):  
Sirisha Reddy Sattinena ◽  
Alex Joseph ◽  
Subham Das ◽  
B Chaitainya ◽  
Subba Rao
Keyword(s):  
Gas Chromatography ◽  
Simultaneous Determination ◽  
Chromatographic Method ◽  
Isopropyl Alcohol ◽  
Limit Of Detection ◽  
Active Pharmaceutical Ingredients ◽  
Residual Solvents ◽  
Pharmaceutical Ingredients ◽  
Gas Chromatographic Method

Background: Presence of residual solvents in pharmaceuticals can be a potential risk factor to human health because of its toxicity. Gas chromatography used for its excellent separation abilities and lower limit of detection. Racecadotril, an antidiarrheal drug, reported having four residual solvents, namely n-Hexane, isopropyl alcohol, toluene and dimethylformamide. Estimation the amount of these solvents in active pharmaceutical ingredients to ensure that they are within the permissible limits as per ICH guidelines necessary. <p> Objective: To develop and validate a new, simple and sensitive gas chromatographic method for simultaneous determination of n-Hexane, isopropyl alcohol, toluene and dimethylformamide in racecadotril. <p> Method: The residual solvents of racecadotril estimated using a gas chromatographic method by direct injection using FID as a detector. This method employed a 30-meter long DB-FFAP nitroterephthalic-acid-modified polyethene glycol column with 0.53 mm in inner diameter and 1 μm film thickness. The separation achieved using nitrogen as the carrier gas at a flow rate of 2.8 mL/min using a split ratio of 1:10. <p> Results: The peak shape for all the residual solvents from racecadotril was symmetric with excellent resolution eluting at reasonable retention time. The limit of detection of n-Hexane, isopropyl alcohol, Toluene and dimethylformamide found to be 6, 27, 14 and 42 ppm respectively. The developed method exhibited excellent linearity for each residual solvents in the range studied. <p> Conclusion: The developed gas chromatographic method is simple, specific, precise, accurate and sensitive. Hence, the method can be successfully used in the pharmaceutical companies and research laboratories for simultaneous determination of residual solvents in racecadotril active pharmaceutical ingredients.

Therapeutic Monitoring of Anticonvulsant Drugs: Gas-Chromatographic Simultaneous Determination of Primidone, Phenylethylmalonamide, Carbamazepine, and Diphenylhydantoin

1975 ◽  
Vol 21 (11) ◽  
pp. 1658-1662 ◽  
Author(s):  
Charles J Least ◽  
George F Johnson ◽  
Harvey M Solomon
Keyword(s):  
Simultaneous Determination ◽  
Standard Method ◽  
Chromatographic Method ◽  
Limit Of Detection ◽  
Internal Standard ◽  
Normal Serum ◽  
Therapeutic Monitoring ◽  
The Mean ◽  
Gas Chromatographic Method

Abstract We describe a sensitive and precise gas-chromatographic method in which benzylmalonate methylester monoamide is used as the internal standard for the simultaneous determination of primidone, phenylethylmalonamide, carbamazepine, and diphenylhydantoin. The trimethylsilyl derivatives of the anticonvulsants are well separated from each other and from normal serum constituents. The lower limit of detection for each drug is 0.5 mg/liter when 1 ml of serum is analyzed. Withinrun precision (CV), established by analysis of 10 replicates, was as follows: primidone (5.4 mg/liter), 2.6%; phenylethylmalonamide (5.5 mg/liter), 1.6%; diphenylhydantoin (6.6 mg/liter), 3.8%; and carbamazepine (10.4 mg/liter), 3.2%. Fifty specimens were analyzed for primidone and 35 for diphenylhydantoin by a standard gas-chromatographic method involving on-column methylation and by the procedure we have developed. The mean value observed for primidone with the on-column alkylation procedure was 9.3 mg/liter and with our procedure was 9.6 mg/liter. When values for our assay were regressed against values for the standard method, the slope of the least-squares line was 0.936, the intercept was 1.00 mg/liter, and r was 0.939. The mean values observed for diphenylhydantoin by on-column methylation and with our procedure were both 12.6 mg/liter. When values for our assay were regressed against the standard method, the slope of the leastsquares line was 0.944, the intercept was 0.3 mg/liter, and r was 0.988

Antipyrine metabolism in man: simultaneous determination of norantipyrine and 4-hydroxyantipyrine in urine by gas chromatography

1980 ◽  
Vol 58 (1) ◽  
pp. 17-21 ◽  
Author(s):  
T. Inaba ◽  
N. E. Fischer
Keyword(s):  
Gas Chromatography ◽  
Simultaneous Determination ◽  
Chromatographic Method ◽  
Internal Standard ◽  
Antipyrine Metabolism ◽  
Drug Oxidation ◽  
Gas Chromatographic Method

A gas chromatographic method was developed to determine metabolites of antipyrine, norantipyrine (NORA), and 4-hydroxyantipyrine in urine using p-methylated NORA as internal standard. This method requires no derivatization and has ample sensitivity to determine these metabolites in urine after ingestion of antipyrine, a compound widely used as a hepatic probe of drug oxidation.

scholarly journals Determination of residual solvents in paclitaxel by headspace gas chromatography

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Khaleel Noorbasha ◽  
Abdul Rahaman Shaik
Keyword(s):  
Ethyl Acetate ◽  
Chromatographic Method ◽  
Isopropyl Alcohol ◽  
Limit Of Detection ◽  
Good Resolution ◽  
Relative Standard ◽  
Limit Of Quantitation ◽  
Gas Chromatographic Method ◽  
Ethyl Amine

Abstract Background A simple and sensitive gas chromatographic method was developed and validated for the simultaneous determination of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine in Paclitaxel. A chromatographic separation was done on DB-624 column, 30 m length × 0.53 mm ID, and film thickness 3 μm, using a flame ionization detector (FID) with gradient column oven temperature program. The injection was carried out in split mode, with a split ratio of 5:1. A mixture of N-methyl-2-pyrrolidinone (contains 1% piperazine) and water in the ratio of 80:20 (v/v) was selected as a diluent to obtain good sensitivity along with the recovery. Results The developed gas chromatographic method offers symmetric peak shape, good resolution of more than 2.0 between the solvent peaks, and the relative standard deviation for replicate injections of all the solvents were found to be not more than 15.0% with reasonable retention time for all the solvents. The limit of detection for methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine was found to be 304.69 ppm, 497.98 ppm, 498.99 ppm, 504.49 ppm, 61.81 ppm, 30.07 ppm, 505 ppm, 73.05 ppm, and 2.09 ppm, respectively. Limit of quantitation of methanol, ethanol, acetone, isopropyl alcohol, dichloromethane, N-hexane, ethyl acetate, tetrahydrofuran, and N,N-diisopropyl ethyl amine was found to be 89.62 ppm, 146.47 ppm, 146.76 ppm, 148.38 ppm, 18.18 ppm, 8.84 ppm, 148.53 ppm, 21.49 ppm, and 0.62 ppm, respectively. Precision was found to be satisfactory. Linear in the range of LOQ to 150% level for all the solvents, and accuracy along with robustness, is performed, and acceptable results were obtained. Conclusion The proposed method was demonstrated to be simple, sensitive, specific, linear, precise, accurate, and robust, hence can be used to determine the residual organic solvents in Paclitaxel drug substance and drug product.

Fast Method for the Determination of Residual Solvents in Radiopharmaceutical Products

2017 ◽  
Vol 68 (4) ◽  
pp. 666-670 ◽  
Author(s):  
Mirela Mihon ◽  
Catalin Stelian Tuta ◽  
Alina Catrinel Ion ◽  
Dana Niculae ◽  
Vasile Lavric
Keyword(s):  
Gas Chromatography ◽  
Control Method ◽  
Limit Of Detection ◽  
The Body ◽  
Biologically Active ◽  
Injection Technique ◽  
Fast Method ◽  
Residual Solvent ◽  
Residual Solvents

The aim of this work was the development and validation of a fast analytical method to determine the residual solvents content in radiopharmaceuticals such as: 18F-Fluorodeoxyglucose (18F-FDG), 18F-Fluoroestradiol (18F-FES), 18F-Fluorothymidine (18F-FLT),18F-Fluoromisonidazole (18F-FMISO). Radiopharmaceuticals are radioactive preparations for medical purposes used in nuclear medicine as tracers in diagnostic imaging and treatment of certain diseases. Positron Emission Tomography (PET) is a medical imaging technique that consists in introducing into the body of a small amount of a biologically active chemical compound labelled with a short lived positron-emitting radioisotope (18F, 11C, 68Ga). Residual solvents are critical impurities in radiopharmaceuticals that can affect labelling, stability and physicochemical properties of drugs. Therefore, the determination of these solvents is essential for quality control of radiopharmaceuticals. Validation of the control method for residual solvents by gas chromatography is referred by the European Pharmacopoeia using a special injection technique (head space). The parameters of the method, which comply with International Conference on Harmonization guidelines, are: accuracy, precision, linearity, limit of detection, limit of quantification and robustness. The proposed method (direct gas chromatography injection) proved to be linear, precise, accurate and robust. Good linearity was achieved for all the solvents and correlation coefficients (R2) for each residual solvent were found more than 0.99.

Gas Chromatographic Determination of N-Butyl-N-ethyl-α,α,α-trifluoro-2,6-dinitro-p-toluidine and α,α,α-Trifluoro-2,6-dinitro-N,N-dipropyl-p-toluidine in Formulations

1971 ◽  
Vol 54 (3) ◽  
pp. 711-712
Author(s):  
Martha Fuzesi
Keyword(s):  
Gas Chromatography ◽  
Quantitative Determination ◽  
Electron Capture ◽  
Chromatographic Method ◽  
Chromatographic Determination ◽  
Electron Capture Detector ◽  
Reference Solution ◽  
Gas Chromatographic Method

Abstract A gas chromatographic method is described for the quantitative determination of N-butyl-N-ethyl-α,α,α-trifluoro-2,6-dinitro-p-tolindine and α,α,α-trifluoro-2,6-dinitro-N,N-dipropyI-p-toluidine herbicides in formulations. The sample is extracted with benzene, and equal amounts of sample and reference solution in the same concentration range are analyzed by gas chromatography, using an electron capture detector and an SE-30/Diatoport S column. The method has been applied successfully to laboratory-prepared and commercial samples.

A Headspace Gas Chromatographic Method for Determination of Formic acid Content in Isosulfan Blue and in Various Drugs

2021 ◽  
Vol 37 (2) ◽  
pp. 321-329
Author(s):  
Nilesh Takale ◽  
Neelakandan Kaliyaperumal ◽  
Gopalakrishnan Mannathusamy ◽  
Rajarajan Govindasamy
Keyword(s):  
Sulfuric Acid ◽  
Formic Acid ◽  
Chromatographic Method ◽  
Isopropyl Alcohol ◽  
Class Iii ◽  
Drug Substances ◽  
Headspace Gas ◽  
Concentrated Sulfuric Acid ◽  
Gas Chromatographic Method

The Pharmaceutical industry uses formic acid in the manufacturing of various drug substances or API. At the time of manufacturing of API formic acid is use as an oxidizing agent. Formic acid is the simplest carboxylic acid. It also called methanoic acid.Formic acid present in API at high concentrations is very hazardous but in low concentrations is very beneficial. The developed and validated method was short, precise, cost effective and reproducible with FID detector and easy to use. The method is a selective and superficial analytical method for determination of formic acid in different drug substances. We report here the development and validation study of headspace gas chromatographic method to determine formic acid in different drug substances we are reported here. As per this method, the drug sample was dissolved in 0.1% (v/v) of concentrated sulfuric acid in isopropyl alcohol (IPA) in a GC headspace vial and 0.1% (v/v) of concentrated sulfuric acid in isopropyl alcohol used as a diluent. A AB-Inowax capillary column (30 m x 0.32 mm I.D. and 0.5 µm film thickness) was used under gradient conditions with FID. The formic acid peak was well separated from all other solvents that are used in synthesis of particular drug substance. The LOD and LOQof the method for formic acid are 82 ppm and 249 ppm respectively. Formic acid are low toxic class-III solvent as per ICH guideline.

scholarly journals The Use of Cryogenic Temperature Gas Chromatography for the Determination of Carbon Monoxide and Carbon Dioxide in Cigarette Smoke

1972 ◽  
Vol 6 (4) ◽  
Author(s):  
G.P. Morie ◽  
C.H. Sloan
Keyword(s):  
Carbon Dioxide ◽  
Gas Chromatography ◽  
Carbon Monoxide ◽  
Liquid Nitrogen ◽  
Cigarette Smoke ◽  
Cryogenic Temperature ◽  
Chromatographic Method ◽  
Porapak Q ◽  
Gas Chromatographic Method

AbstractA gas chromatographic method for the determination of carbon monoxide and carbon dioxide in cigarette smoke was developed. A column containing Porapak Q packing and a cryogenic temperature programmer which employed liquid nitrogen to cool the column to subambient temperatures was used. The separation of N

Simultaneous Determination of Emtricitabine and Tenofovir disoproxil fumarate in Pharmaceutical Dosage by Reverse Phase High Performance Liquid Chromatography

2021 ◽  
pp. 412-416
Author(s):  
Rajan V. Rele ◽  
Sandip P. Patil
Keyword(s):  
High Performance Liquid Chromatography ◽  
Liquid Chromatography ◽  
Simultaneous Determination ◽  
Tenofovir Disoproxil Fumarate ◽  
High Performance ◽  
Phosphoric Acid Solution ◽  
Active Pharmaceutical Ingredients ◽  
Chromatography Method ◽  
Pharmaceutical Ingredients

A simple, rapid and accurate high performance liquid chromatography method is described for simultaneous determination of emtricitabine and tenofovir disoproxil fumarate from active pharmaceutical ingredients. The separation of drug was achieved on Hypersil BDS C18 (150 x 4.6 mm i.d.) with 5 µ particle size column showed most favorable chromatographic pattern over the other columns. The mobile phase consisted of a mixture of buffer and methanol (85:15 % v/v). The buffer was mixtures of 0.1 % (v/v) ortho-phosphoric acid solution adjusted the pH 3.5 with tri-ethyl amine. The detection was carried out at wavelength 260 nm. The mixture of buffer of pH 3.5 and methanol (85:15% v/v) was used as a diluent. The method was validated for system suitability, linearity, accuracy, precision, robustness, stability of sample solution. The method has been successfully used to analyze emtricitabine and tenofovir disoproxil fumarate from active pharmaceutical ingredients.

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