title: Determination of 2-Hydroxypyridine-1-Oxide (HOPO) at sub-ppm levels using derivitization and gas chromatography with mass spectrometry detection (GCMS).
abstract: This work describes the development and validation of an analytical method to determine residual trace levels of 2-Hydroxypyridine-1-Oxide (HOPO) in an active pharmaceutical ingredient (API). A method was required to be specific and sensitive enough to determine sub-ppm levels of this reagent. The approach taken to use a derivitization step overcame two of the primary challenges associated with the analysis of HOPO. Firstly, HOPO can tautomerize and the derivitization step provides a single stable entity to monitor, and secondly, the reaction enhances the volatility of the analyte to facilitate the use of gas chromatography. Mass spectrometry detection provides both suitable specificity and sensitivity. This paper describes the method development and optimisation of the derivitization step, the chromatographic conditions and mass spectrometry detection, together with a summary of the validation of the method. The method has been demonstrated to be robust and suitable to determine HOPO levels in commercially manufactured API materials.
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, CH46 1QW, United Kingdom. Electronic address: emma.quirk@bms.com.
authors: Emma
authors: E
authors: Quirk
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, CH46 1QW, United Kingdom.
authors: Catrin
authors: C
authors: Davies
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, CH46 1QW, United Kingdom.
authors: Paul
authors: P
authors: Foy
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, CH46 1QW, United Kingdom.
authors: Alison
authors: A
authors: Bretnall
authors: Bristol-Myers Squibb Pharmaceuticals, Reeds Lane, Moreton, CH46 1QW, United Kingdom.
authors: Graham S
authors: GS
authors: Clarke
mesh_terms: D003497:Cyclic N-Oxides / Q000737:chemistry*; D008401:Gas Chromatography-Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000737:chemistry*; D011725:Pyridines / Q000737:chemistry*; D012680:Sensitivity and Specificity
chemical_list: C547041:2-hydroxypyridine-N-oxide; D003497:Cyclic N-Oxides; D004364:Pharmaceutical Preparations; D011725:Pyridines
keywords: 2-Hydroxypyridine-1-Oxide (HOPO); Derivitization; Gas chromatography; Mass spectrometry quantitification; Trace analysis; Validation