For the characterization of solid state materials, numerous advantages exist with molecular spectroscopy: qualitative and quantitative analysis, real-time monitoring of transient species, the ability to study API or drug product, and process analytical technology (PAT) application. Due to these advantages, we apply molecular spectroscopy for both standard compendial methodology and high-end research applications. Because of our wide range of spectroscopic instrumentation, we can apply the appropriate technology to your needs.

Infrared and Raman Spectroscopy

We perform solid state analyses with state-of-the-art infrared (IR), near IR (NIR) and Raman spectrometers. Each of these techniques can provide both qualitative characterization of different solid forms and a means to quantitate the solid form composition within the drug substance or product.

  • Infrared spectroscopy
    • Diffuse reflectance
    • Alkyl halide pellet
    • Mineral oil mull
    • TG/IR
    • Microspectroscopy
    • Variable temperature diffuse reflectance
    • Variable humidity diffuse reflectance
    • Attenuated total reflectance
    • Grazing angle
    • Chemical mapping
  • NIR spectroscopy imaging
  • Raman spectroscopy
    • Dispersive and FT-Raman spectrometers
    • Microspectroscopy
    • Chemical mapping
    • Variable temperature

UV/Visible Spectroscopy

We apply ultraviolet/visible absorption spectroscopy in support of dissolution, stability and solubility studies.

NMR Spectroscopy

We perform both solid state and liquid state cGMP nuclear magnetic resonance (NMR) spectroscopy to characterize a wide variety of materials from small inorganic compounds to large molecules (polymers, unmodified and modified peptides, proteins, DNA, RNA). We have the capabilities to analyze specific nuclei like 19F in both solids and liquids because they are present in about 20 percent of pharmaceutical drugs. We also have NMR capabilities for analyzing large molecule biologics, which are the fastest growing type of molecules currently being developed as drugs. NMR spectroscopy delivers higher resolution and sensitivity with modern solids with as little as 10 mg of sample required.

Our experts provide customized data interpretation for maximum value and flexibility. We conduct our studies in full cGMP compliance with U.S. and European regulations to ensure the highest quality data, interpretation and experimental consistency.

We provide a complete suite of capabilities with small molecule, synthetic polymer and biologics NMR spectroscopy:

  • 2D NMR analyses such as COSY, NOESY, TOCSY, HMQC, HSQC and HMBC with peak assignments of specific resonances to provide detailed information on molecular structure and conformation in solution
  • Compendial NMR methods in accordance with EP or USP/NF specifications
  • Qualitative and quantitative NMR (qNMR) method development and validation for all available NMR techniques; most of our validated methods are used for clinical or commercial lot release or stability studies
  • Comparability and sameness studies of biologics due to the sensitive and accurate fingerprint of the molecular conformation extracted from the NMR data
  • Identification and quantitation of known and unknown impurities
  • Characterization of polymorphs, solvates, salts, cocrystals and amorphous solids
  • Chemical structure identification (solids and liquids)
  • Analysis of formulations (solids and liquids)
  • Analysis of stereoisomers (solids and liquids)
  • Determination of the number of molecules in an asymmetric unit (solids)
  • Chemical exchange analysis (solids and liquids)
  • Molecular motion analysis (solids and liquids)
  • Conformational/structural analysis (solids and liquids); 3D chemical structure determination of small molecules and biologics using NMR restrained molecular dynamics (MD) simulations
  • 300−500 MHz NMR spectrometers, some of which can analyze both solids and liquids

Liquid State NMR

We offer liquid state NMR spectroscopy to determine molecular structure and conformation as well as analyze specific components in a mixture either qualitatively or quantitatively. Solution NMR spectroscopy provides a sensitive method to quantify impurities, reaction products or residual solvents including water. A large variety of methods for NMR spectroscopy of liquid solutions is available at 400 MHz (1H). Variable temperature experiments are also available for liquid NMR analyses. Some of the most common analyses include 1D NMR of 1H, 13C, 19F and 31P NMR. We also perform more advanced 2D NMR analyses. We apply these techniques to determine the assignments of specific resonances for a molecule, which can provide the necessary information to obtain a molecular conformation in solution.

  • 5 mm double resonance pulsed field gradient (PFG) probe for high sensitivity on the X and Y channels (useful for typical small organic molecules and biologics)
  • 5 mm inverse detection PFG probe (useful for biologics and typical small organic samples)
  • 5 mm dual broadband PFG probe (ideal for organic and inorganic materials to observe 13C, 15N, and other lower frequency nuclei or those nuclei with low natural abundance)
  • Z-axis gradient capabilities for performing many of the newest pulsed field gradient experiments
  • Wide range of 2D NMR spectroscopic techniques available for structural elucidation
  • Variable temperature capabilities from -80 °C to 130 °C
  • Sample quantities in ~0.5 mL solvent
  • 1H or 19F – 0.1-5 mg, 31P – 10-20 mg, 13C – 20-50 mg

Solid State NMR

Solid state NMR spectroscopy is useful for analyzing polymorphs, solvates, salts, cocrystals, amorphous solids and formulations. We perform high-resolution solid state NMR spectroscopy at 400 MHz (1H) for most of the NMR active nuclei on the periodic table. Variable temperature experiments can be performed from -75°C to 100°C.

We conduct standard direct excitation or enhancement via ramped amplitude cross-polarization, modulated high-power proton decoupling, very high-speed spinning (up to 18 kHz), spectral editing and spinning sideband suppression. Our capabilities and technologies include:

  • Agilent T3 narrow-bore double and triple resonance 4 mm solid state NMR probes
  • Doty Scientific 4 mm HF probe specifically designed for simultaneous 1H decoupling while detecting 19F or the reverse
  • Doty Scientific 4 mm HFX probe specifically designed for simultaneous 1H decoupling while detecting 19F or X nuclei or 19F decoupling while observing X
  • Low frequency: Observe any NMR active nucleus with a resonance frequency between 15N (~40 MHz) and 31P (~162 MHz)
  • High frequency: Observe or decouple 1H (~400 MHz) and 19F (~376 MHz) nuclei
  • MAS and CP/MAS available up to 18 kHz spinning speed (with modern phase modulated decoupling and/or TOSS spinning sideband suppression) to offer the highest data quality
  • Simultaneous 1H and 19F decoupling while observing on the X-channel or 1H decoupling while observing 19F
  • 2D correlation spectroscopy of common nuclei (1H, 13C, 15N, 19F, 29Si, 31P)
  • 2D MQMAS or STMAS of quadrupolar nuclei
  • Variable temperature capabilities from -75 °C to 100 °C
  • Sample quantities: 40−50 mg (optimal), 5−10 mg (possible)