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Looking closely.

The Spectroscopy Section of the Drug Identification Division is responsible for molecular spectroscopic characterization of drugs, precursors, by-products, excipients, and metabolites by means of NMR, MS, and IR spectroscopy. In addition to the vast range of ethical drugs that are examined in both bulk and formulated form, considerable effort has been expended over the years in characterizing novel illicit substances (e.g. designer drugs and other new street drugs), anabolic steroids, foreign medicaments introduced to Canada by returning tourists and minority cultural groups, botanical preparations, and chemical substances in general. The section, headed by George A. Neville, FCIC, is comprised of Brian A. Dawson in charge of nuclear magnetic resonance (NMR) spectroscopic operations, Jiri Zamecnik supported by Jean-Claude Ethier responsible for mass spectroscopic determinations, D. Bruce Black who provides backup operation for both these areas as well as conducting liquid chromatographic separations, and Harry D. Beckstead who is responsible for the FT-IR instrumentation and attendant spectroscopic analyses.

Much of the work here is undertaken in support of research activities by other divisions of the Bureau of Drug Research, other bureaux of the Drugs Directorate, and occasionally for one or more of the five Regional Laboratories, the Food Directorate, and other Departments. Centralization of such molecular spectroscopic service is justified because of the high capital cost of the sophisticated instrumentation, the specialized expertise required for its operation and interpretation of spectral output, as well as the appreciable annual operating costs. The supporting services range anywhere from good laboratory practice (GLP) certification of the authenticity of chemical substances to be studied for toxicological and/or pharmacological properties to outright collaboration with individual or teams of research scientists in the structural elucidation of a drug metabolite, botanical extract, or submitted unknowns.

Our instrumentation consists of a Brucker AM 400 NMR spectrometer with a superconducting magnet fully equipped for multi-nuclear studies, one- and two-dimensional (1-D and 2-D) capabilities, and other sophisticated operations. An older Bruker WP80 NMR spectrometer is used for routine 1H and 13C analysis including those for WHO and Pharmacopoeial studies which specify 100 MHz or less. For mass spectroscopic analyses, either via the gas-chromatographic (GC) or direct exposure probe (DEP) routes, we have a Finnigan 4610 instrument with spectral library searching capability for some 180,000 compounds. An older Finnigan 4500 instrument was recently assembled and paired with the 4610 for routine MS analysis as well as for possible future modification for LC-MS analyses. Our Nicolet 60 SX Fourier transform infrared (FT-IR) spectrometer and data system is equipped with a capillary GC-IR optical bench including a more sensitive MCT detector to permit useful and sensitive headspace gas analyses to be done. In addition to regular IR sampling in the form of KBr discs, Nujol/fluorolube split mulls, and solution cells, we are able to perform diffuse reflectance infrared fourier transform spectroscopy (DRIFTS) on substances whose nature would be altered by the compression required to form KBr discs (e.g: polymorphs). Other accessories include a circle cell, useful as a flow-through cell for HPLC/IR and for dilute aqueous solutions by multiple internal reflection, and an attenuated total reflectance (ATR) kit for surface studies. The data system, with a library searching capability for some 40,000 compounds, permits comparison and subtraction of spectra particularly useful for the identification of mixtures, excipients, and inorganic substances.

Research activity by section members is, by necessity, interspersed and secondary to their work; however, opportunity for research endeavour does exist through collaborative undertakings and spin-off investigations arising from mission-oriented tasks. One aspect of the section's responsibility that illustrates this duality is in the area of authentication of illicit drugs for court purposes. Usually house standards are referenced to recognized USP or NIDA reference standards when such are available; however, when such reference materials are not available, the in-house standards must be fully structurally characterized, and the results of such work are publishable. Similarly, even with older drugs, such as morphine, we have found opportunity to publish high-resolution 1H-NMR spectral analysis of morphine and its three O-acetylderivatives, the O3, O6-diacetyl derivative being heroin.

Considerable NMR work has been done over the past four years by Dawson, since joining the section, in structural characterization of new designer amphetamines as well as in the use of chiral shift reagents to differentiate between optical isomers of both ethical and illicit drugs while simultaneously obtaining molecular spectroscopic evidence to verify the authenticity of the examined substances. Since joining the Section nearly two years ago, Zamecnik has developed a GC-MS method using n-butylboronic acid for derivatizing and quantifying [Beta]-adrenergic blocking agents and bronchodilator compounds in biological materials. Together with Ethier and Black, he has determined levels of mono- and di-(2-ethylhexyl) phthalate in human serum albumin. Beckstead together with Neville, developed a very effective GC-FTIR headspace analytical method for detection and identification of trace solvents in cocaine for intelligence purposes The headspace method was used to identify the ethyl acetate complex of O6-acetylmorphine in the course of FT-IR characterization of this complex versus its uncomplexed substrate and other acetylated morphine compounds.

More recently, there has been collaboration with A.S Perlin, FCIC, of McGill University in NMR studies of regular commercial heparin preparations and of various low molecular weight (LMW) heparin derivatives. In' collaboration with P Rochon and T.J. Racey of the Royal Military College of Canada, Kingston, Ont., particle size studies of the heparin materials were undertaken. In collaboration with H.F. Survell at Queen's University, Neville has studied various 1, 4-benzodiazepine compounds by a combined FT-IR/FT-Raman technique.

The section must cope with materials of diverse nature; it must be flexible to accommodate new and ever changing priorities; and it must strive to achieve its expected share of publishable research while also fulfilling service and other mission-oriented tasks. It's not an easy function, but it's a wonderfully dedicated section.
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Title Annotation:Canada's Bureau of Drug Research Spectroscopy Section
Author:Neville, George A.
Publication:Canadian Chemical News
Date:Nov 1, 1989
Words:970
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