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Published on: August 22, 2017
Stable isotopic composition of the active pharmaceutical ingredient (API) naproxen
A M Wokovich1, J A Spencer, B J Westenberger
1Food and Drug Administration, Center for Drug Evaluation and Research, Division of Pharmaceutical Analysis, St. Louis, MO 63101, USA. wokovicha@cder.fda.gov
Journal of Pharmaceutical and Biomedical Analysis
|June 22, 2005
Summary
Isotope Ratio Mass Spectrometry (IRMS) can identify the manufacturer of the pharmaceutical naproxen. Analyzing carbon, oxygen, and hydrogen isotopes revealed distinct isotopic fingerprints for most manufacturers, enabling provenance screening.
Area of Science:
- Analytical Chemistry
- Pharmaceutical Analysis
Background:
- Active Pharmaceutical Ingredients (APIs) require robust methods for provenance verification.
- Distinguishing API sources is crucial for quality control and regulatory compliance.
Purpose of the Study:
- To evaluate the utility of Isotope Ratio Mass Spectrometry (IRMS) for determining the manufacturing origin of naproxen.
- To assess the multi-stable isotopic composition of naproxen as a potential identifier of API provenance.
Main Methods:
- Analyzed twenty-six naproxen lots from six manufacturers across four countries.
- Measured carbon (delta13C), oxygen (delta18O), and hydrogen (deltaD) isotope ratios using Elemental Analyzer/IRMS (EA/IRMS) and Thermal Conversion-EA/IRMS (TCEA/IRMS).
Main Results:
- Distinct isotopic clustering was observed for five out of six naproxen manufacturers.
- Bivariate and trivariate isotope ratio plots demonstrated manufacturer-specific patterns.
- The D/H, delta13C, and delta18O isotope ratios showed potential for distinguishing API sources.
Conclusions:
- IRMS analysis of stable isotopes provides a viable method for screening the manufacturer of naproxen.
- Isotopic composition serves as a reliable fingerprint for API provenance verification.
- This technique offers a promising approach for ensuring pharmaceutical supply chain integrity.
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