Stable isotopic composition of the active pharmaceutical ingredient (API) naproxen.
A survey of the multi-stable isotopic composition of an active pharmaceutical ingredient (API), naproxen, was performed to assess the potential of Isotope Ratio Mass Spectrometry (IRMS) to distinguish the provenance of APIs. Twenty-six lots of naproxen from six manufacturers representing four countries (Italy, India, Ireland, and the USA) were analyzed for three isotope ratios (13C/12C, 18O/16O, and D/H). The samples were analyzed by either Elemental Analyzer/Isotope Ratio Mass Spectrometry (EA/IRMS: carbon (delta13C)) or by Thermal Conversion-EA/IRMS (TCEA/IRMS: hydrogen (deltaD) and oxygen (delta18O)). Bivariate and trivariate isotope ratio graphs for naproxen show marked clustering of the data for five out of the six naproxen manufacturers, suggesting that IRMS may be a plausible means to screen for manufacturer of given APIs.
Wokovich
A M
AM
Food and Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, St. Louis, MO 63101, USA. wokovicha@cder.fda.gov
Spencer
J A
JA
Westenberger
B J
BJ
Buhse
L F
LF
Jasper
J P
JP
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000032:analysis*; D002247:Carbon Isotopes; D006859:Hydrogen / Q000032:analysis; D013058:Mass Spectrometry; D009288:Naproxen / Q000032:analysis*; D010103:Oxygen Isotopes; D015203:Reproducibility of Results; D014481:United States; D014486:United States Food and Drug Administration
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002247:Carbon Isotopes; D010103:Oxygen Isotopes; D009288:Naproxen; D006859:Hydrogen