Control and Analysis of Genotoxic Impurities in Drug Substance Development

2014 ◽  
pp. 384-403
Keyword(s):  
Drug Substance ◽  
Genotoxic Impurities

scholarly journals Low Level Quantification of Potential Genotoxic Impurities In Telmisartan Drug Substance by HPLC

2021 ◽  
Vol 11 (3) ◽  
pp. 24-35
Author(s):  
K. Srivalli ◽  
N. Annapurna ◽  
K. Raghu Babu ◽  
C. Ramdas ◽  
Hemant Kumar Sharma ◽  
...  
Keyword(s):  
Drug Substance ◽  
Low Level ◽  
Genotoxic Impurities

scholarly journals A SELECTIVE AND SENSITIVE LC-MS/MS METHOD FOR QUANTIFICATION OF FOUR POTENTIAL GENOTOXIC IMPURITIES IN ATAZANAVIR SULFATE DRUG SUBSTANCE IN TRACE LEVEL

2021 ◽  
pp. 137-144
Author(s):  
SIVA JYOTHI N. ◽  
VENKATNARAYANA MUVVALA
Keyword(s):  
Mobile Phase ◽  
Multiple Reaction Monitoring ◽  
Research Work ◽  
Active Pharmaceutical Ingredient ◽  
Drug Substance ◽  
Genotoxic Impurities ◽  
Liquid Chromatography Tandem Mass ◽  
Short Run ◽  
Acquity Uplc ◽  
Atazanavir Sulfate

Objective: The main objective of current research work is to develop and validate a rapid, sensitive and selective liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the trace analysis of four potential genotoxic impurities in Atazanavir Sulfate drug substance. Methods: LC-MS/MS analysis of four potential genotoxic impurities was done on Acquity UPLC CSH C18 (100 mm × 2.1 mm, 1.7 μm) column. In this method, mobile phase A (10 mM ammonium acetate) mobile phase B (methanol: acetonitrile (90:10, v/v) with gradient run with the flow rate of 0.2 ml/min. The method was developed with the short run time of 13 min. Triple quadrupole mass detector coupled with positive electrospray ionization was used for the quantification of genotoxic impurities in multiple reaction monitoring (MRM) mode. Results: The method was linear in the range of 0.3 ppm to 4.5 ppm for BOC Hydrazine Acid impurity, BOC Epoxide and Keto impurity with a correlation coefficient not less than 0.9994. The accuracy of the method was in the range of 99.26% to 105.71% for all four potential genotoxic impurities (PGIs). No impurities were identified in the Atazanavir Sulfate active pharmaceutical ingredient sample. Conclusion: The proposed method is specific, linear, precise, accurate, robust and stable for the quantification of the four genotoxic impurities at very low levels.

Detection of Two Genotoxic Impurities in Drug Substance and Preparation of Imatinib Mesylate by LC–MS/MS

2020 ◽  
Vol 83 (7) ◽  
pp. 821-828
Author(s):  
Dong Wang ◽  
Lijun Luo ◽  
Yue Peng ◽  
Jing Wang ◽  
Jing Liang ◽  
...  
Keyword(s):  
Imatinib Mesylate ◽  
Drug Substance ◽  
Genotoxic Impurities

scholarly journals DEVELOPMENT AND VALIDATION OF SEVEN PHENYL HYDRAZINE CHLORO ESTER ISOMERS (PGIs) BY RP-HPLC-UV METHOD IN ANTICOAGULANT DRUG SUBSTANCE; APIXABAN

2020 ◽  
pp. 119-123
Author(s):  
SARADHI VENKATA RAMANA V. ◽  
DURGA RAJA K. ◽  
RAGHU BABU K. ◽  
PADMA M. ◽  
JAGADEESH KUMAR V. ◽  
...  
Keyword(s):  
Mobile Phase ◽  
Hplc Method ◽  
Point Of View ◽  
Drug Substance ◽  
Accurate Analysis ◽  
Intermediate Precision ◽  
Chromatography Method ◽  
Rp Hplc ◽  
Genotoxic Impurities ◽  
Anticoagulant Drug

Objective: The objective of this work was to develop and validate a simple and sensitive reverse-phase high-pressure liquid chromatography method for the determination of seven potential genotoxic impurities in Apixaban drug substance. Methods: The optimized separation was achieved by using ACE 3 C18 PFP (150 mm×4.6 mm, 3 µm) HPLC column. The mobile phase-A was a degassed mixture of 0.01M Ammonium acetate buffer(PH adjusted 4.9±0.05 with diluted glacial acetic acid) and mobile phase-B was a degassed mixture of Acetonitrile, Isopropyl alcohol and Buffer PH 4.9 in the ratio of 60:20:20 v/v/v. The gradient program was operated at a flow rate of 1.0 ml/min and UV detection was at 330 nm. Results: The method was superior at linearity for seven impurities and correlation coefficient values were larger than 0.999, moreover, in the separation point of view, this method further achieved no matrix interference through chromatography by better resolution of the other impurities from the Apixaban drug substance and its related impurities for the accurate analysis of seven potential genotoxic impurities. The established limits of detection (LOD), limits of quantification (LOQ) values for the seven mutagenic impurities were each of 5 ppm (0.015µg/ml) and15 ppm (0.045µg/ml) respectively. The developed method was validated as per ICH guidelines and applied as a generic method to determine these seven potential genotoxic impurities for the pharmaceutical process control and drug material release. Conclusion: Validation of this analytical method was carried out including stability, selectivity, linearity, accuracy, system precision, method precision and intermediate precision thus proving that the described RP-HPLC method could be employed for fast and simple analysis of sevenphenyl hydrazine chloro ester isomers in Apixaban drug substance.

scholarly journals ULTRA-HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC DETERMINATION OF GENOTOXIC IMPURITIES IN FEBUXOSTAT DRUG SUBSTANCE AND PRODUCTS

2016 ◽  
Vol 10 (1) ◽  
pp. 324
Author(s):  
Balaji N ◽  
Sayeeda Sultana
Keyword(s):  
High Performance ◽  
Limit Of Detection ◽  
Chromatographic Determination ◽  
High Performance Liquid Chromatographic ◽  
Drug Substance ◽  
Internal Diameter ◽  
Liquid Chromatograph ◽  
Limit Of Quantitation ◽  
Genotoxic Impurities ◽  
Liquid Chromatographic

ABSTRACTObjective: An efficient ultra-high performance liquid chromatographic (UHPLC or Infinity LC 1290) method has been developed and validated for thequantification of possible carcinogenic or genotoxic impurities in febuxostat drug substances and drug products at 18 µg/ml level.Methods: This method includes the conclusion of four potential genotoxic impurities in febuxostat. The mobile phase is trifluoroacetic acid,acetonitrile, and water with linear gradient elution. The UHPLC column used for the analysis was zorbax RRHD eclipse plus C18 with a length of100 mm, internal diameter of 2.1 mm, and particle size of 1.8 µ.Results: The limit of detection and limit of quantitation of the impurities are <0.1 (0.00001%) and 0.3 µg/ml (0.00003%) with respect to febuxostattest concentration of 1000 µg/ml, respectively. This method has been validated as per ICH guidelines Q2 (R1).Conclusion: A rapid, cost-effective infinity LC method was wonderfully established for quantitative analysis of possible genotoxic impurities offebuxostat drug substance and drug products.Keywords: Febuxostat, Genotoxic impurities, Ultra-high performance liquid chromatograph, Infinity-LC 1290, Validation.

scholarly journals A Validated GC-MS Method for the Determination of Genotoxic Impurities in Divalproex Sodium Drug Substance

2018 ◽  
Vol 57 (2) ◽  
pp. 101-107
Author(s):  
S Raghavender Reddy ◽  
K Hussain Reddy ◽  
M Narendra Kumar ◽  
P Madhava Reddy ◽  
J Venkata Ramana Reddy ◽  
...  
Keyword(s):  
Drug Substance ◽  
Divalproex Sodium ◽  
Genotoxic Impurities

scholarly journals A Selective and Sensitive Method for Simultaneous Quantification of Genotoxic Impurities in Penciclovir drug substance and its dosage forms using UPLC-MS/MS

2020 ◽  
Vol 11 (4) ◽  
pp. 5772-5776
Author(s):  
Rao P.Y.G ◽  
Sreenivasa Rao B ◽  
Suresh Reddy K.V.N ◽  
Sudhakar Ch
Keyword(s):  
Limit Of Detection ◽  
High Sensitivity ◽  
Dosage Forms ◽  
Drug Substance ◽  
Ich Guidelines ◽  
Validation Parameters ◽  
Genotoxic Impurities ◽  
Chromatographic Parameters ◽  
Sensitive Method ◽  
Bromo Compound

A selective, rapid and sensitive method was developed for the determination of genotoxic impurities (2-Amino-6-chloro purine and Bromo compound) in Penciclovir drug substance using RPUPLC-MS/MS. The chromatographic separation was performed on Kromasil C8 column (150 mm x 4.6 mm, 5 μm) maintained at 45°C using 0.1%formic acids in water as buffer and acetonitrile through gradient programme. The flow rate was maintained at 0.5mL/min with an injection volume of 10 μL. For the quantification of genotoxic impurities, positive-electrospray ionisation (ESI) mode was selected. Penciclovir and its impurities were well separated within the shortest run time of 16min. The chromatographic method was developed, and the results of all validation parameters showed that the technique is well confined to the limits of ICH guidelines. The method has high sensitivity, and the limit of detection was found to be as low as 0.15 and 0.30 ppm for 2-Amino-6-chloro purine and Bromo compound. The recovery of 2-Amino-6-chloro purine and Bromo compound are found in the range of 80-120%. The linearity of peak area versus concentration was demonstrated in the range of LOQ - 150% level of impurities with a correlation coefficient of 0.9999. The method has proved too robust by introducing minuscule changes in the chromatographic parameters. The method was successfully validated and applied for Penciclovir drug substances and their dosage forms to determine the mentioned genotoxic impurities.

Sign in / Sign up

Export Citation Format

Share Document