title: Rapid and simultaneous determination of sulfonate ester genotoxic impurities in drug substance by liquid chromatography coupled to tandem mass spectrometry: comparison of different ionization modes.
abstract: Two ionization techniques for liquid chromatography-mass spectrometry (LC-MS) determination of sulfonate ester potentially genotoxic impurities (PGIs) were evaluated. Twelve PGIs including methyl, ethyl, propyl and isopropyl esters of methanesulfonate, benzenesulfonate and p-toluenesulfonate were studied in this research. Electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) sources were compared in terms of performance and quality parameters for detection of the twelve PGIs. Their mass spectra obtained by APCI and ESI were very different in both fragment ions and relative abundances. In APCI negative ion mode the twelve sulfonate esters showed their stable precursor ions of [M-alkyl](-), which readily yielded product ions of [M-alkyl-CH3](-) (for aliphatic sulfonate esters) or [M-alkyl-SO2](-) (for aromatic sulfonate esters) with collision-induced dissociation (CID) applied; and working in selected reaction monitoring (SRM) mode has allowed limits of detection to be decreased. In the case of ESI ionization, these compounds showed their precursor ions [M+H](+), but their abundance was easily competed by formation of ions [M+NH4](+) and/or [M+Na](+), which led to poor analytical sensitivity and reproducibility. Although mobile phase additives could enhance the responses of adduct ions like [M+NH4](+) and [M+Na](+), no improvement was obtained when using SRM mode. Twelve sulfonate esters were systematically compared and APCI was shown to be a better ionization technique for rapid and sensitive determination of these PGIs. Performance of the developed approach for rapid determination of 12 PGIs was also evaluated. Quality parameters were established and good precision (relative standard deviations <8%) and very low limits (2-4ng/mL) of detection were obtained, mainly when using APCI in SRM mode.
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Tian
authors.initials: T
authors.lastname: Guo
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Li
authors.initials: L
authors.lastname: Zheng
authors.affiliation: Department of Natural Medicine Chemistry, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Feng
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: cpu_analyst@126.com.
authors.forename: Feng
authors.initials: F
authors.lastname: Zheng
authors.affiliation: Department of Pharmaceutical Analysis, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China; Key Laboratory of Drug Quality Control and Pharmacovigilance, Ministry of Education, China Pharmaceutical University, 24 Tongjiaxiang, Nanjing 210009, China. Electronic address: liuwenyuan8506@163.com.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Liu
mesh_terms: D002412:Cations / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D004952:Esters / Q000737:chemistry*; D009153:Mutagens / Q000737:chemistry / Q000302:isolation & purification*; D015203:Reproducibility of Results; D013451:Sulfonic Acids / Q000737:chemistry / Q000302:isolation & purification*; D053719:Tandem Mass Spectrometry / Q000295:instrumentation / Q000379:methods*; D013997:Time Factors
chemical_list: D002412:Cations; D004952:Esters; D009153:Mutagens; D013451:Sulfonic Acids
keywords: Atmospheric pressure chemical ionization; Comparison of ionization modes; Electrospray ionization; Rapid and simultaneous determination; Sulfonate esters