scholarly journals Development and validation of gas chromatography methods for the control of volatile impurities in the pharmaceutical substance dutasteride

2016 ◽  
Author(s):  
Aleksandra Groman ◽  
Elżbieta U. Stolarczyk ◽  
Marta Jatczak ◽  
Elżbieta Lipiec-Abramska
Keyword(s):  
Gas Chromatography ◽  
Carbon Tetrachloride ◽  
Direct Injection ◽  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Experimental Conditions ◽  
Limit Test ◽  
Development And Validation ◽  
Optimization Of Experimental Conditions ◽  
Volatile Impurities

Dutasteride, N-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is an active pharmaceutical ingredient (API) which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride as a 5-reductase inhibitor is useful for the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Because of a large variety of solvents and reagents used in the synthesis, it was necessary to develop new, sensitive and selective gas chromatography (GC) methods. The optimization of the methods consisted in selecting different types of sample injection and detection as well as optimization of experimental conditions that allowed to meet the appropriate range (10-120% of the specification limit) and suitable detection limits (LOD) of compounds. Significant differences in the volatility of these compounds forced the division into volatile solvents (methanol, acetonitrile, dichloromethane, ethyl acetate, heptane and toluene) analyzed with the use of the gas chromatography with headspace (GC-HS) and less volatile compounds (pyridine, dimethylformamide, 1,4-dioxane, acetic acid, ethylene glycol, 4-dimethylaminopyridine) analyzed with the use of gas chromatography with direct injection (GC-FID). Benzene, carbon tetrachloride and 1,2-dichloroethane are potential contaminants of toluene and dichloromethane, thus the control of these solvents was a limit test procedure. Due to the low specification limits for benzene (2 ppm), carbon tetrachloride (4 ppm) and 1,2-dichloroethane (5 ppm) it was neccesery to use gas chromatography with mass spectrometry detection (GC-MS). All three new methods were validated according to the requirements of the ICH (International Conference on Harmonization) validation guideline Q2R1 and the guideline for residual solvents Q3C. Specificity, precision, accuracy, linearity, limits of detection and quantitation and robustness were determined and the results meeting the acceptance criteria were obtained.

scholarly journals Development and validation of gas chromatography methods for the control of volatile impurities in the pharmaceutical substance dutasteride

2016 ◽  
Author(s):  
Aleksandra Groman ◽  
Elżbieta U. Stolarczyk ◽  
Marta Jatczak ◽  
Elżbieta Lipiec-Abramska
Keyword(s):  
Gas Chromatography ◽  
Carbon Tetrachloride ◽  
Direct Injection ◽  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Experimental Conditions ◽  
Limit Test ◽  
Development And Validation ◽  
Optimization Of Experimental Conditions ◽  
Volatile Impurities

Dutasteride, N-[2,5-Bis(trifluoromethyl)phenyl]-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide, is an active pharmaceutical ingredient (API) which inhibits the conversion of testosterone to dihydrotestosterone. Dutasteride as a 5-reductase inhibitor is useful for the treatment of benign prostatic hyperplasia (BPH) and prostate cancer. Because of a large variety of solvents and reagents used in the synthesis, it was necessary to develop new, sensitive and selective gas chromatography (GC) methods. The optimization of the methods consisted in selecting different types of sample injection and detection as well as optimization of experimental conditions that allowed to meet the appropriate range (10-120% of the specification limit) and suitable detection limits (LOD) of compounds. Significant differences in the volatility of these compounds forced the division into volatile solvents (methanol, acetonitrile, dichloromethane, ethyl acetate, heptane and toluene) analyzed with the use of the gas chromatography with headspace (GC-HS) and less volatile compounds (pyridine, dimethylformamide, 1,4-dioxane, acetic acid, ethylene glycol, 4-dimethylaminopyridine) analyzed with the use of gas chromatography with direct injection (GC-FID). Benzene, carbon tetrachloride and 1,2-dichloroethane are potential contaminants of toluene and dichloromethane, thus the control of these solvents was a limit test procedure. Due to the low specification limits for benzene (2 ppm), carbon tetrachloride (4 ppm) and 1,2-dichloroethane (5 ppm) it was neccesery to use gas chromatography with mass spectrometry detection (GC-MS). All three new methods were validated according to the requirements of the ICH (International Conference on Harmonization) validation guideline Q2R1 and the guideline for residual solvents Q3C. Specificity, precision, accuracy, linearity, limits of detection and quantitation and robustness were determined and the results meeting the acceptance criteria were obtained.

scholarly journals Development and Validation of 2-Azaspiro [4,5] Decan-3-One (Impurity A) in Gabapentin Determination Method Using qNMR Spectroscopy

Molecules ◽  
2021 ◽  
Vol 26 (6) ◽  
pp. 1656
Author(s):  
Nataliya E. Kuz’mina ◽  
Sergey V. Moiseev ◽  
Mikhail D. Khorolskiy ◽  
Anna I. Lutceva
Keyword(s):  
Test Procedure ◽  
Active Pharmaceutical Ingredient ◽  
Test Methods ◽  
Intermediate Precision ◽  
Coefficients Of Variation ◽  
Validation Parameters ◽  
Limit Of Quantitation ◽  
Student’S T ◽  
Development And Validation ◽  
Student’S T Test

The authors developed a 1H qNMR test procedure for identification and quantification of impurity A present in gabapentin active pharmaceutical ingredient (API) and gabapentin products. The validation studies helped to determine the limit of quantitation and assess linearity, accuracy, repeatability, intermediate precision, specificity, and robustness of the procedure. Spike-and-recovery assays were used to calculate standard deviations, coefficients of variation, confidence intervals, bias, Fisher’s F test, and Student’s t-test for assay results. The obtained statistical values satisfy the acceptance criteria for the validation parameters. The authors compared the results of impurity A quantification in gabapentin APIs and capsules by using the 1H qNMR and HPLC test methods.

Sign in / Sign up

Export Citation Format

Share Document