Abstract from :

The SMi Conference on "Securing the Pharmaceutical Supply Chain" Meeting
(London, UK; November 29-30, 2004)
The International Isotope Society Meeting
(King of Prussia, PA; October 29, 2004)
The American Chemical Society’s Meeting on Pharmaceutical Authentication and Forensic Analysis
(May 25-27, 2004; Tampa, Florida)

Multi-Stable-Isotopic Authentication of Pharmaceutical Identity

J. P. Jasper1, L. Buhse2, B. Westenberger2, A. Wokovich2, J. Spencer2, F. Fourel3,
A. Eaton3, J. Morrison3, A. Phillips3, L. E. Weaner4, and B. Duffy4

1Molecular Isotope Technologies, LLC, Old Oak Lane, Niantic, CT 06357-1815 USA
2FDA-Division of Pharmaceutical Analysis, St. Louis, MO USA
3GV Instruments, UK
4Johnson & Johnson Pharmaceutical Research and Development
Welsh and McKean Roads, Spring House, PA USA
Pharmaceutical product security is currently viewed in a tripartite system spanning from Overt to Covert to Forensic technologies. Forensic (or Analytical) technologies are authentication or security measures that require the use of laboratory equipment in their application. Here we focus on the use of naturally-occurring, non-radioactive stable isotopes as they are found in pharmaceutical components in their ambient concentrations. Typically-measured isotope ratios include those of carbon (13C/12C), oxygen (18O/16O), hydrogen (D/H), and nitrogen (15N/14N). They are typically measured on an automated Elemental Analyzer/Isotope Ratio Mass Spectrometer (EA/IRMS). Here, we report on the stable isotopic characterization of suites of: (i) Four over-the-counter analgesic drug products [performed with GV Instruments, UK; Pharm. Tech., 2004, 28(8):60-67]; (ii) Four active pharmaceutical ingredients [(APIs; J. Pharm. Biomed. Anal., 2004, 35(1):21-30]; (iii) Six APIs from four countries (FIRMS Newsletter, 2004, 2(1):3). (Both ii and iii were performed with the FDA-Division of Pharmaceutical Analysis, St. Louis, MO USA.); and, (iv) A single API (Topiramate) which were produced by three synthetic pathways and which were subsequently analyzed in a preliminary investigation of the use of stable isotopes to differentiate those pathways for use in patent protection [with Johnson & Johnson Pharmaceutical Research and Development; FIRMS Newsletter, 2004, 2(2):8-9].

Many such studies often show that there is a highly-specific "isotopic fingerprint" (typically, 1 in millions-billions) which defines the "isotopic provenance" for pharmaceutical materials. Scientifically, isotopes provide identity for those materials. In application, they can be used to mitigate counterfeiting, diversion, theft, vicarious liability, and patent infringement.

Stable isotopic characterization of APIs and other pharmaceutical materials provides an innate and highly-specific identification for pharmaceutical products. Nothing is added to the pharmaceutical materials, thus avoiding a regulatory challenge regarding natural isotopic composition. In fact, customized isotopic labeling of pharmaceutical materials can be achieved by quantitative mixing of components of known isotopic composition in known proportions as defined by the laws of mass balance and isotope mass balance.