A gas chromatographic method for the indirect determination of hydroxylamine in pharmaceutical preparations: conversion into nitrous oxide.
A simple, sensitive, and selective headspace gas-chromatographic method has been developed for measuring hydroxylamine (HA) in a variety of sample matrices including pharmaceutical formulations. This procedure relies on converting HA into nitrous oxide (N2O), which is a single-step reaction that is carried out directly in a heated headspace vial. The gaseous products are then analyzed by headspace capillary gas chromatography. Several detection strategies were evaluated and electron capture provided the best sensitivity (4 parts-per-billion (ppb)) while the mass selective and thermal conductivity values were higher (14 ppb and 1.4 parts-per-million (ppm), respectively). The method's linear dynamic range spans two to four decades with a run-to-run precision that was better than 5% R.S.D. (n=7). The reagent concentrations (oxidant, buffer) strongly impact the N2O signal and the greatest response was obtained for solutions that contained equimolar amounts of reactants. HA was efficiently (98%) recovered from a sample matrix that contained only the active pharmaceutical ingredient (API) but the recovery was lower (83%) when excipients were present.
Guzowski
J P
JP
Bristol-Myers Squibb, Pharmaceutical Research Institute, 1 Squibb Drive, New Brunswick, NJ 08903, USA. john.guzowski@bms.com
Golanoski
C
C
Montgomery
E R
ER
D002849:Chromatography, Gas / Q000379:methods; D019811:Hydroxylamine / Q000032:analysis* / Q000378:metabolism; D009609:Nitrous Oxide / Q000032:analysis* / Q000378:metabolism; D004364:Pharmaceutical Preparations / Q000032:analysis
D004364:Pharmaceutical Preparations; D019811:Hydroxylamine; D009609:Nitrous Oxide