title: Sensitive derivatization methods for the determination of genotoxic impurities in drug substances using hyphenated techniques.
abstract: Six sensitive derivatization methods for the determination of genotoxic impurities in selected drug substances were developed using hyphenated techniques. Some of the raw materials, reagents and reaction intermediates of the selected drug substances were identified as genotoxic impurities through DEREK software for windows. The genotoxic impurities which are amenable for derivatization were selected as substrates. Derivatizing agents were selected based on the functional groups of the genotoxic impurities. The chemistry involved in the derivatization was explained with suitable mechanisms. An appropriate hyphenated technique viz. LC-MS and GC-MS was opted based on the sensitivity and aromaticity of the derivatized genotoxic impurities. All the methods were validated as per International Conference on Harmonization guidelines. Correlation coefficient values were found about 0.99. The obtained % R.S.D values from replicate injections in the range of 2.3-4.8 and % recoveries of the added impurities in the range of 83.7-101.7 ensured the precision and accuracy, respectively.
authors: Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India. Electronic address: raman@heterodrugs.com.
authors: Nanduri V V S S
authors: NV
authors: Raman
authors: Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India. Electronic address: prasad.a@heterodrugs.com.
authors: Adapa V S S
authors: AV
authors: Prasad
authors: Hetero Drugs Ltd. (R&D), Plot No. B. 80 & 81, APIE, Balanagar, Hyderabad 500018, India.
authors: Kura Ratnakar
authors: KR
authors: Reddy
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods; D004340:Drug Contamination; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D007202:Indicators and Reagents / Q000737:chemistry; D013058:Mass Spectrometry / Q000379:methods; D009153:Mutagens / Q000737:chemistry*; D004364:Pharmaceutical Preparations / Q000737:chemistry*
chemical_list: D007202:Indicators and Reagents; D009153:Mutagens; D004364:Pharmaceutical Preparations
keywords: DEREK; Derivatization; Drug substances; Genotoxins; Hyphenated techniques