title: A Simple and Direct LC-MS Method for Determination of Genotoxic Impurity Hydroxylamine in Pharmaceutical compounds.
abstract: Hydroxylamine is a known genotoxic impurity compound that needs to be controlled down to ppm level in pharmaceutical processes. It is difficult to detect using conventional analytical techniques due to its physio-chemical properties like lack of chromophore, low molecular weight, absence of carbon atom and high polarity. In addition to that, analysis of the pharmaceutical samples encounters considerable obstruction from matrix components that greatly overshadow the response of hydroxylamine. This study describes a simple, sensitive and direct Liquid Chromatographic-Mass Spectrometric method (LC-MS) for detection of hydroxylamine in pharmaceutical compounds. The LC-MS method was detected up to 0.008 ppm of hydroxylamine with S/N > 3.0 and quantified up to 0.025 ppm of hydroxylamine with S/N ratio >10.0. This validated method can be applied as a generic method to detect the hydroxylamine for pharmaceutical process control and drug substance release.
authors.affiliation: Analytical Research and Development Division, Piramal Enterprises Limited, Chennai 600057, India.|Department of Chemistry, St Josephs College, Trichirappalli 620001, India.
authors.forename: Thangarathinam
authors.initials: T
authors.lastname: Kumar
authors.affiliation: Department of Genetic Engineering, SRM University, Kattankulathur, Chennai 603203, India.
authors.forename: Mohandass
authors.initials: M
authors.lastname: Ramya
authors.affiliation: Analytical Research and Development Division, Piramal Enterprises Limited, Chennai 600057, India.
authors.forename: Viswanathan
authors.initials: V
authors.lastname: Srinivasan
authors.affiliation: Department of Chemistry, St Josephs College, Trichirappalli 620001, India.
authors.forename: N
authors.initials: N
authors.lastname: Xavier
mesh_terms: D002853:Chromatography, Liquid / Q000379:methods*; D004340:Drug Contamination; D019811:Hydroxylamine / Q000032:analysis*; D057230:Limit of Detection; D016014:Linear Models; D013058:Mass Spectrometry / Q000379:methods*; D009153:Mutagens / Q000032:analysis*; D015203:Reproducibility of Results
chemical_list: D009153:Mutagens; D019811:Hydroxylamine