Nuclear Magnetic Resonance (NMR)

NMR (nuclear magnetic resonance) spectroscopy has long been an invaluable analytical method in industry for verification of chemical synthesis and compound characterization. The power of NMR spectroscopy is truly unparalleled in the arena of structural identification of organic and biochemical compounds. In combination with other services already offered by Exova,  including Fourier Transform Infrared Spectroscopy (FTIR), elemental analysis and mass spectrometry, NMR will prove particularly useful to projects aimed at identification of chemical and pharmaceutical unknowns. Our NMR services are targeted primarily to corporate customers in the biotechnology, pharmaceutical, specialty chemical, nutraceutical, personal care, oil and petrochemical industries.

NMR - Introduction

Our NMR System

NMR Services

NMR GMP Compliance

Example NMR Applications


For a quotation......


NMR - Introduction

NMR spectroscopy uses radiofrequency radiation to induce transitions between different nuclear spin states of samples in a magnetic field. NMR spectroscopy can be used for quantitative measurements, but it is most useful for determining the structure of molecules (along with FT-IR and mass spectrometry). The utility of NMR

spectroscopy for structural characterization arises because different atoms in a molecule experience slightly different magnetic fields and therefore transitions at slightly different resonance frequencies in an NMR spectrum. Furthermore, splittings of the spectral lines arise due to interactions between different nuclei, which provides information about the proximity of different atoms in a molecule. A typical NMR spectrum is shown in Figure 1.

 

 

NMR spectrum of Strychnine


Our NMR System

The NMR system was installed in the Santa Fe Springs facility in December 2008 and operates at 500 MHz (resonance frequency for 1H). It has capabilities to study 1H and other nuclei (13C, 31P, 29Si, 19F, 2H, etc.). The NMR spectrometer is capable of analyzing samples in solution state (by the majority of modern 1D and 2D NMR experiments) and in solid state (by CP/MAS, cross polarization/magic-angle-spinning spectroscopy). The instrument has variable

temperature capabilities (ranging from -80 °C to +150 °C for solutions, and from -45 °C to +110 °C for solids).

Figure 2 is an example of the main components of the NMR spectrometer, namely, the superconducting magnet, the console holding the electronics, and the computer workstation. The connectors for the various nuclei on the two probe heads (the 'antennas') are depicted in the bottom insets. The probe heads are inserted at the bottom; the sample, in an NMR glass tube (see top inset), is injected at the top of the magnet.

NMR spectrometer

Figure 2. NMR spectrometer with peripherals. Insets: Probe heads and NMR sample tube.

 


NMR Services

We offer a number of “routine” NMR services, ideal for product quality control, structure verification, structure elucidation of smaller molecules and/or evaluation of compound purity (including, for example, the purity check of heparin, recently mandated by FDA , as well as any other NMR tests mentioned in USP and EP monographs). Examples of solution-state NMR experiments in this category are:

·    1D spectra of 1H, 13C, 19F and 31P

·    2D {1H,1H} COSY, TOCSY and 2D {1H,13C} HSQC and HMBC

 

Solid-state NMR is commonly used in the analysis of polymorphs, particularly in the pharmaceutical area. Our routine solid-state NMR services will include CP/MAS spectra of 13C, 29Si, 31P etc. We also look forward to assisting customers who have needs for more advanced NMR applications aimed at, for example, complete characterization of compounds of modest structural complexity.

Exova’s NMR services are expected to benefit a wide range of customers in chemistry, biochemistry, pharmacy, life sciences, and material sciences. More specifics can be found in the April 2010 issue of Analytical Digest.

Please contact Nic Preece 562-948-2225 (ext 614) if you have any questions regarding NMR services that may be of interest to your company.


NMR GMP Compliance

Exova believes that it has one of the very few GMP compliant NMR systems existing in a commercial laboratory. GMP compliance starts with documented procedures such as a Standard Operating Procedure (SOP) for operation and maintenance, instrument run logs, and sample preparation logs. The system is qualified annually for instrument parameters such as sensitivity,

resolution, line shape, and pulse width for various nuclei. The instrument software has been validated for file security to 21 CFR Part 11 standards. Operators are qualified through documented training.

While the system is used for several GMP compendial tests, Exova also provides research, method development and validation according to ICH guidelines


Example NMR Applications

In addition to extensive structure proof and R&D experitise, Exova is capable of providing data according to the following standardized methods.  Links to applicable web pages on some of these topics are provided.

  1. Biopolymers such as PLGA, identification, monomer content, and residual monomers
  2. Heparin according to latest USP monograph, identification, analysis for oversulfated chondroitin sulfate, and other impurities
  3. Poloxamer, weight % oxyethylene
  4. Chitosan, degree of deacetylation
  5. Silicone - polydimethylsiloxane
  6. Quantitative 13C NMR of polyethylene and polypropylene
  7. NMR for QC of Aloe Vera
  8. NMR and Polymer Tacticity

 For a quotation......

NMR - Pharmaceutical and Medical Device Applications
Standard Methods (USP, EP, and ASTM)

Material

Application

Monographs

 

General NMR Method

USP<761>
EP 2.2.33
ASTM E386

Alginate

Chemical composition and sequential structure, 1H and 13C

ASTM F2259

Amyl Nitrite

Identification, 1H

USP

Buserelin

Identification, 1H

EP

Chitosan

Degree of deacetylation, 1H

ASTM F2260

Cod-Liver Oil

Identification, 13C
Positional distribution (
b(2)-acyl) of fatty acids

EP

Enoxaparin

Identification, 13C

USP

Goserelin

Identification, 13C

EP

Heparin

Identification, 1H
Impurirty OSCS, 1H

USP, EP

Hydroxypropyl Betadex

Molar substitution, 1H

USP, EP

Lauromacrogol

Average chain length of fatty alcohols and moles of ethylene oxide, 13C

EP

Medronic Acid

Identification, 1H
Impurities, 1H

EP

Orphenadrine Citrate

Isomer content, 1H

USP

Oxytocin

Identification, 1H

USP

Poloxamer (polyoxyethylene polyoxypropylene)

Weight % Oxyethylene, 1H

USP

Polylactide and glycolide Identification, residual monomer, lactide/glycolide ratio, 1H and 13C

 

ASTM F2579,
F1925, F2313

Polyoxyl 10 Oleyl Ether (polyethylene glycol monomethyl ether)

Average polymer length, 1H

USP

Polyoxyl 20 Cetostearyl Ether

Average polymer length, 1H

USP

Salmon Oil

Identification, 13C
Positional Distribution (
b(2)-acyl) of fatty acids

EP

Simethicone

Identification, 1H , 29Si-filtered 1H, 2D {1H, 29Si}

 


For a full listing of Exova services, please visit our new Exova web site,  Exova Pharmaceutical Solutions web site and our new Santa Fe Springs laboratory home page.

Exova

9240 Santa Fe Springs Rd
Santa Fe Springs, CA 90670
562.948.2225   Fax 562.948.5850
info400@exova.com

Exova

Formerly West Coast Analytical Service (WCAS) and Bodycote Testing Group