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February 2002 Meeting |
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The Use of Naturally-Existing Stable Isotopes in Pharmaceuticals To Maintain Product Integrity |
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Date: | Tuesday, February 26, 2002 | |||||||
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Location: | Bristol-Myers
Squibb Wallingford, CT. |
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Speaker: | John
P. Jasper Molecular Isotope Technologies |
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Agenda: | 5:30-6:30
PM Registration/Social Hour 6:30-7:30 PM Dinner 7:30-8:30 PM Presentation |
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Cost: | $25 ($5 Students and Emeritus) | |||||||
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Registration Deadline: |
Friday, February 22, 2002 | |||||||
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| Abstract: Counterfeiting
of pharmaceutical drugs threatens the efficacy of and consumer confidence
in these products, as well as the economic well-being of pharmaceutical
companies. Bulk isotopic analyses of batch samples of drug products is a
highly-specific means of identifying these materials as they leave
manufacturers and enter the marketplace. Characterization of the ambient
batch-to-batch stable isotopic variation of these products represents a
means by which to “fingerprint” individual drug batches.
Samples of four over-the-counter analgesics were powdered and their isotope ratios were measured by continuous-flow isotope-ratio mass spectrometry using Micromass’ IsoPrime MS. Stable isotopic analyses of oxygen, hydrogen, and carbon were performed on each of the forty-three samples to evaluate each of their δ18O, δ D, and δ 13C compositions. As an example, consider the oxygen isotopic data: they range from 5.1 to 24.3‰ vs. VPDB, spanning 19.2‰. The probability of the isotopic composition of two batches from independent sources being the same is inversely proportional to the product of the ‘dynamic ranges’ of the isotopic analyses undertaken (where the dynamic range is defined as the range of values expected for a given type of measurement divided by the standard deviation of that measurement). With a pooled estimate of standard deviation of 0.16‰ for the present δ 18O analyses, the dynamic range for this suite of samples is 120. Possible explanations for the observed isotopic variations include natural variation in the raw starting materials and isotopic fractionation during the synthetic processing of the active pharmaceutical ingredients in the drugs. The specificity (or, composite dynamic range) of Isotopic Product Integrity can be analogously estimated. For example, if four isotopic compositions were measured on a given product and the dynamic range of each isotope was 100, the specificity would be (1/100)4 or, 1 in 108. That is, the possibility of that product being randomly counterfeited would be about 1 in 108. It would be significantly more costly to synthesize a given product with specific isotopic values than it would be to purchase the original material, especially since the fingerprint changes with virtually every batch! We conclude that a combination of isotopic analyses of given samples will provide highly-specific characterization of drug batches and will allow for the tracing of the origin of pharmaceuticals. This approach should minimize the effects of counterfeiting and international countertrading of pharmaceutical products, as well as vicarious liability to the host firm. |
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| Biography: Dr.
John P. Jasper is an analytical, organic and stable isotope chemist who
uses bulk and compound-specific approaches to determine the sources of
natural and synthetic organic matter, particularly drug substances and
drug products. He is the
Chief Scientific Officer of Molecular Isotope Technologies (MIT, LLC; www.MolecularIsotopes.com)
and the Managing Partner of Arson Stable Isotope Analysis (ASIA), a joint
venture of MIT, LLC and EFT Analytical Chemistry, Inc. a chemical forensic
firm. He earned a B.A. in
Geophysical Sciences and in Biological Sciences at the University of
Chicago in 1981. He earned a
Ph.D. in marine organic chemistry from the Massachusetts Institute of
Technology/Woods Hole Oceanographic Institution Joint Program in Chemical
Oceanography in 1988. In his
Ph.D. thesis, he assessed the relationship between the elemental and
isotopic compositions of bulk organic phases and contemporaneous specific
organic compounds to quantify the effects of glacial-interglacial climatic
change on the distribution of organic matter in the deep ocean (Jasper
& Gagosian, 1990, 1993). As
a postdoctoral fellow and scientist at the Department of Chemistry at
Indiana University, he co-developed a method by which to reconstruct
pre-existing dissolved CO2 levels in ancient oceans (Jasper
& Hayes, 1990) spanning the last ~250,000 years.
This method is useful in establishing the natural CO2(g)
baseline for quantifying Greenhouse effects on climate.
A recent application of the alkenone-isotopic approach spanned the
last 25 million years. While
at Pfizer, Inc.-Cultor, Inc., he worked on the separation and
quantification of complex mixtures of synthetic fats (Jasper, 2000).
He founded the company that became Molecular Isotope Technologies,
LLC in 1998. The company
works with major pharmaceutical companies, focusing on the use of stable
isotopes in pharmacology, particularly Isotope Product Integrity (IPI) and
in drug metabolism (Jasper, 1999, 2001).
By 2001, he and colleagues had shown that virtually every lot or
batch of pharmaceuticals had their own “isotopic fingerprints.”
ASIA shows promise in linking (via “isotopic fingerprinting”)
accelerants splashed on arson suspects to accelerants found at arson
scenes (Jasper et al., 2002 and
MIT, LLC website).
Jasper,
J.P., Edwards, J.S., Ford, L.C., and Corry, R.A. (2002). Putting the
Arsonist at the Scene: "DNA" for the Fire Investigator? Gas
Chromatography/Isotope Ratio Mass Spectrometry.
Fire Arson Investig.
51(2):30-34. |
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| Directions:
Bristol-Myers
Squibb Company From the South (New York) I-95 Northbound to Exit 48 in New Haven which is the beginning of I-91 North. Get off Exit 15 from I-91 and take right at the traffic light onto Route 68 East. Take a left at the first traffic light onto Research Parkway, which is about 3/10 of a mile from the exit. The Wallingford facility is the first building on the right. From the North I-91 Southbound to Exit 15. Take left at light at end of ramp. Take left at second traffic light (approximately 1/2 mile) onto Research Parkway. The Wallingford facility is the first building on the right. Via Route 15 (Hutchinson River/Merritt/Wilber Cross Parkways) Exit 66 in Wallingford. Turn left at light at the end of the ramp onto Route 5 Southbound. Stay on Route 5 for approximately 1/2 mile and make left immediately past the Shell station onto the access road for Route 68. Turn left at light onto Route 68 (Eastbound). Follow Route 68 East past the Courtyard Hotel on the left and continue past the entrances to I-91.Turn left at the first traffic light past I-91 (not including the entrance to I-91 Northbound) onto Research Parkway. Bristol-Myers Squibb is the first building on the right. Via I-95 (New England Expressway) Take I-95 (Northbound) to Exit 48 (left exit) onto I-91 (Northbound). Stay on I-91 for about 15 miles to Exit 15 (Route 68). Turn right off Exit 15 onto Route 68 (Eastbound towards Durham). Turn left at first traffic light onto Research Parkway. Bristol-Myers Squibb is the first building on the right. |
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