A preliminary multi-stable isotopic evaluation of three synthetic pathways of topiramate

The Network developingforensic applications of stable Copy of research articlepublished in September issue of the FIRMS Newsletter:
(FIRMS Newsletter, 2004,
A Preliminary Multi-Stable Isotopic Evaluation of Three
2(2): 8 – 9)
Synthetic Pathways of Topiramate
J. P. Jasper1 , L. E. Weaner2, and B. J. Duffy2 Molecular Isotope Technologies LLC, 8 Old Oak Lane, Niantic, Connecticut 06357-1815 USA; Johnson & Johnson Pharmaceutical Research and Development, L.L.C., Welsh and McKean Roads, PO Box776, Spring House, Pennsylvania 19477-0776 USA.
Pharmaceutical products can be characterized or “fingerprinted” by measuring and comparingtheir highly-specific stable isotopic ratios via isotope-ratio mass spectrometric analysis (Jasper,2004; Jasper et al., 2004, and refs. therein). The isotopic composition observed is dependent onboth the reactants used and the manufacturing process employed. A change in either of thesevariables produces a drug product having a different isotopic profile. Recent work has shown thatwhen both the source of the starting materials and the manufacturing process are presumably heldrelatively constant during manufacture of the bulk drug substance, similar product isotopic-ratiosare observed (Jasper et al., 2004). By measuring the isotopic ratios for suspect samples in casessuch as drug counterfeiting and process patent infringement, it may be possible to obtain usefulinformation about the process and origin of raw materials used.
Fig.1. Structure of Topiramate (C12H21NO8S).
To test the utility of the natural stable-isotopic differentiation of batch samples produced bydifferent pathways, multi-stable isotopic analyses (d13C, d15N, d18O, and dD) of 53 Topiramate samples produced by three different synthetic pathways (designated “A,” “B,” and “C”) wereperformed (Fig. 1). Examination of the data via the six possible bivariate isotope plots, revealsdistinct data clustering, though in some cases with some overlapping within standard errors. Ingeneral, the isotopic composition of Topiramate from the C pathway is distinct from those of theA and B pathways. The isotopic data from the A and B pathways typically abut each other,sometimes partially overlapping. The hydrogen/deuterium- (dD) and oxygen (d18O) isotopic compositions of Topiramate are each significantly linearly correlated with the paired carbon(d13C) isotopic composition (Fig. 2). Given that H and O largely derive from meteoric water, the linear correlations with d13C indicate that a mixture of carbon sources (viz., perhaps terrestrial C3 photosynthetic organic carbon and marine C3 organic carbon) were used in the production of thebatches tested. If the H and O analyzed derived from meteoric water, then an elementarycomparison of the span of the dD (DdD = 54.6 + 2.1‰) and d18O (Dd18O = 4.71 + 0.26‰) values in the Topiramate samples to the global isotopic gradients indicates that the water retained in thesamples spanned from as much as 11o of latitude (or, ~760 statute miles north to south). Thepresent isotope results (d13C, d15N, d18O, and dD) form a database against which future samples can be compared to infer specific synthetic pathways. Topiramate: d13C vs dD
C (13d
dD (‰ vs VPDB)
Fig. 2. A bivariate isotope plot (d13C vs. dD) of 53 Topiramate samples produced by three References
Jasper, J. P. (2004) "Pharmaceutical Security: Using Stable Isotopes to Authenticate Pharmaceutical Materials. Tablets Capsules, 2(3):37-42.
Jasper, J. P., B. J. Westenberger, J. A. Spencer, L. F. Buhse, and M. Nasr (2004). Stable isotopic characterization of active pharmaceutical ingredients. J. Pharm. Biomed. Anal. 35(1):21-30

Source: http://www.naturesfingerprint.com/pdfs/FIRMS2(2)8-9.pdf


000_b.fm Page 1 Monday, September 17, 2007 4:55 PMNel migliore dei mondi possibili, la pubblicazione di questo li-bro scuoterebbe come un terremoto il dibattito italiano su Internete le nuove tecnologie di comunicazione. Se non produrrà nemme-no uno scarto, significa che quel dibattere è una parvenza di vita,finestre sbattute dal vento in una villa disabitata, mortorio al cuiconfronto un polte


(Saguraku- enena--- sinonim rijeÄ i saguraku- koji se kod Zeamija joÅ¡ uvijek oznaÄ ava kao Noumjetnost. RijeÄ enen- doslovno, produžetak života, nekad je oznaÄ avala skup plesovaizvoÄ enih u budistiÄ kim hramovima povodom praznika, a saguraku je tkÄ . bio dio programa. Tokom godina stekla uže znaÄ enje- obredni ples pojedinih hramova)Kad se veliko božanstvo povuklo u svoj k

Copyright ©2018 Drugstore Pdf Search