Determination of Potentially Genotoxic Impurities in Crotamiton Active Pharmaceutical Ingredient by Gas Chromatography

2021 ◽  
Author(s):  
Andrea Kalauz ◽  
Imre Kapui
Keyword(s):  
Gas Chromatography ◽  
Active Pharmaceutical Ingredient ◽  
Genotoxic Impurities

scholarly journals SIMULTANEOUS DETERMINATION OF 2-CHLORO METHYL PROPIONATE, 1,4-DI-BROMO BUTANE AND PARA ANISIC ALDEHYDE IN MEBEVERINE HYDROCHLORIDE API BY GAS CHROMATOGRAPHY-MASS SPECTROMETRIC WITH SELECTED-ION-MONITORING MODE

2016 ◽  
pp. 168
Author(s):  
Mannem Durga Babu ◽  
Surendrababu K ◽  
Uma Maheswar K
Keyword(s):  
Gas Chromatography ◽  
Limit Of Detection ◽  
Mass Spectrometric ◽  
Spectrometric Method ◽  
Mass Spectrometric Method ◽  
Selected Ion Monitoring ◽  
Methyl Propionate ◽  
Genotoxic Impurities ◽  
Pharmaceutical Industries

<p>ABSTRACT<br />Objective: To develop an accurate, precise and linear gas chromatography-mass spectrometric (GC-MS) selected-ion-monitoring (SIM) method for<br />quantitative estimation of 2-chloro methyl propionate (2-CMP), 1,4-dibromo butane and para anisic aldehyde (PAA) as an genotoxic impurities in<br />mebeverine HCl API (MEB) at ppm level and validated as per International Council of Harmonization (ICH) guidelines.<br />Methods: This method used in SIM mode mass selective detection was developed and validated for the trace level analysis of three impurities. All<br />these three impurities are simultaneously determined by a GC-MS method using VF-624 Capillary column (60 m×0.32 mm×1.80 µm) with Helium as<br />carrier gas and a flow rate of 2.0 mL/minutes. Chromatographic separation of 2-CMP, 1,4-DBB, and PAA was achieved in 7.91, 13.69, 18.45 minutes<br />and m/z values were 63, 55, 135 on SIM mode.<br />Results: The method was linear for 2-CMP, 1,4-DBB and PAA in mebeverine HCl 1.90 µg/ml to 7.5 µg/ml, respectively. The coefficient of correlation<br />(r<br />) for the 2-CMP, 1,4-DBB and PAA was better than 0.999. The limit of detection obtained was 0.28, 0.35, 0.22 µg/ml and the limit of quantification<br />(LOQ) obtained was 0.85, 1.06, 0.66 µg/ml. The method was fully validated, complying Food and Drug Administration, ICH and European Medicines<br />Agency guidelines. Furthermore, verified precision, accuracy, LOQ precision, LOQ accuracy, ruggedness, and robustness.<br />2<br />Conclusion: The proposed method is specific, accurate, precise, linear, rugged and robust for the determination of the three genotoxic impurities in<br />API of mebeverine HCl, and hence, is of wide applicability in pharmaceutical industries.<br />Keywords: 2-chloro methyl propionate, 1,4-dibromo butane, Para anisic aldehyde, Mebeverine HCl, Gas chromatography-mass spectrometric, Method<br />development, Method validation.</p>

scholarly journals Method Development for the Control of Potential Genotoxic Impurities in Vigabatrin Using Gas Chromatography Techniques and Mass Spectroscopy Detector

2021 ◽  
pp. 422-429
Author(s):  
D. Srikanth ◽  
S. Ganapaty ◽  
P. Manik Reddy ◽  
K. Sunitha ◽  
G. Sowjanya
Keyword(s):  
Method Development ◽  
Signal To Noise Ratio ◽  
Active Pharmaceutical Ingredient ◽  
Internal Diameter ◽  
Selected Ion Monitoring ◽  
Intermediate Precision ◽  
Quality Control Testing ◽  
Genotoxic Impurities ◽  
Headspace Gc

Aim: To develop a sensitive headspace GC-MS method for the determination of potential genotoxic impurities in Vigabatrin. Place and Duration of Study: The study was performed in SIONC Pharmaceuticals, Visakhapatnam from June 2020 to March 2021. Methodology: The impurities were determined by selected ion monitoring mode using VF -WAXms (30 mts length, 0.25 mm internal diameter, 1.0 µ film thickness) column. Helium gas was used as carrier gas with a column flow of 1.0 mL/min. and injector temperature maintained at 220 0C. Oven Temperature, loop temperature and transfer line temperature were maintained in the head space at 70oC, 90oC and 100oC respectively. Results: The linearity of the method was proposed in the range of LOQ to 150 % for the genotoxic impurities by subjecting the data obtained to statistical analysis using linear regression model (r2 > 0.99). The method also gave acceptable recovery of all the four impurities at each level and was found to be accurate. The % RSD obtained in the method precision and intermediate precision were less than 11% depicting the precision of the method. The LOD and LOQ values were calculated based on the signal to noise ratio and are indicating the sensitivity of the method. The specificity of the method was checked for blank interference at the retention time of respective impurities. Conclusion: The results proved that the proposed headspace GC-MS method for the study of potential genotoxic impurities of Vigabatrin was sensitive, precise and accurate and could be routinely used in the quality control testing of the active pharmaceutical ingredient.

Determination of sulfonate ester genotoxic impurities in imatinib mesylate by gas chromatography with mass spectrometry

2016 ◽  
Vol 39 (18) ◽  
pp. 3558-3563 ◽  
Author(s):  
Chaozheng Zhang ◽  
Lin Huang ◽  
Zhiguo Wu ◽  
Chuanyou Chang ◽  
Zhidong Yang
Keyword(s):  
Mass Spectrometry ◽  
Gas Chromatography ◽  
Imatinib Mesylate ◽  
Genotoxic Impurities ◽  
Sulfonate Ester

scholarly journals Low Level Determinations of Methyl Methanesulfonate and Ethyl Methanesulfonate Impurities in Emtricitabine Active Pharmaceutical Ingredient by LC/MS/MS using Electrospray Ionization

2011 ◽  
Vol 6 ◽  
pp. ACI.S6471 ◽  
Author(s):  
P.R. Kakadiya ◽  
T.G. Chandrashekhar ◽  
S. Ganguly ◽  
D.K. Singh ◽  
V. Singh
Keyword(s):  
Electrospray Ionization ◽  
Limit Of Detection ◽  
Multiple Reaction Monitoring ◽  
Active Pharmaceutical Ingredient ◽  
Case Method ◽  
Limit Of Quantification ◽  
Low Level ◽  
Quality Control Tool ◽  
Genotoxic Impurities

Alkyl methanesulfonates have been highlighted as potential genotoxic impurities (PGIs). A sensitive LC/MS/MS method was developed and validated for the determination of Alkyl methanesulfonate impurities in Emtricitabine API (active pharmaceutical ingredient). LC/MS/MS method on Zorbax SB C18 column (150 × 4.6 mm i.d.), 3.5 μm, with electrospray ionization (ESI) in multiple reaction monitoring (MRM) mode was used. The proposed method was specific, linear, accurate, rugged and precise. The calibration curves showed good linearity over the concentration range of 0.0025 μg/ml to 0.3 μg/ml the correlation coefficient was >0.999 in each case. Method had very low limit of detection (LOD) and limit of quantification (LOQ) as 0.3 μg/g and 0.4 μg/g respectively for both the analytes. Accuracy was observed within 80%-120% for both the analytes. This method can be further extended a good quality control tool for low level quantitation of Alkyl methanesulfonate impurities in other API.

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