Understanding isotopic process parameters can be useful in process-patent protection applications. With a full description
of a given pharmaceutical synthetic pathway, the isotopic differences between any precursor and another precursor or a precursor
and the final product can be predicted or at least provisionally understood in principle. This provides valuable insight into
which synthesis process was used. Consistencies in expected isotopic matrix values can provide important information about
process counterfeiting.
Summary
Stable-isotopic fractionations resulting from isotope effects are usually large compared with the precision of isotopic measurements.
These fractionations significantly modulate the isotopic compositions that would be observed if isotopic compositions of starting
materials were the only controlling factor. The fractionations depend not only on the magnitudes of isotope effects associated
with the synthetic reactions used, but also on reaction conditions, specifically those affecting the extent to which reactants
are converted to products. Because of these phenomena, the final isotopic composition of a manufactured product is directly
related to the synthetic scheme used. Subsequently, process analytical chemistry using stable-isotopic analysis can be useful
not only for product authentication, but also for process monitoring or reconstructing the processes by which the product
was synthesized.
Acknowledgments
The concepts of both stable-isotopic product and process authenticity are covered under either existing or pending patents
in either the United States or in G7 countries and Australia owned by Molecular Isotope Technologies LLC. This paper is dedicated
to medical-surgical team at UCSD's Thornton Medical Center.
John P. Jasper, PhD,* is the chief scientific officer of Nature's Fingerprint Authentication, a Division of Molecular Isotope Technologies LLC,
8 Old Oak Lane, Niantic, CT 06357, jpjasper@naturesfingerprint.com
, tel. 860.739.1926, fax 860.739.3250. Larry E. Weaner, PhD, is a senior research fellow with Johnson & Johnson Pharmaceutical Research and Development (Spring House, PA). John M. Hayes, PhD, is a scientist emeritus with Woods Hole Oceanographic Institution (Woods Hole, MA).
*To whom all correspondence should be addressed.
Submitted: Nov. 3, 2006. Accepted: Dec. 27, 2006.
Key words: isotope fractionation, process analytical chemistry, PAC, process patent protection, stable isotopes, synthesis.
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