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Friday, March 6, 2020

1H T Edited 13C CPMAS Spectra - Pharmaceutical Analysis

Active pharmaceutical ingredients (API's) are often mixed with other compounds (excipients) used to dilute, stabilize, sweeten, color, flavour, bind, coat (etc...) the medication.  Often the API is a crystalline compound while the excipients are noncrystalline or amorphous.  When analyzing pharmaceutical pills by solid-state 13C CPMAS NMR, one often wants to observe the active crystalline API and not the amorphous non-active excipients.  This can sometimes be accomplished by collecting spectra with differing recycle delays, as the excipients often have shorter 1H T1 relaxation times than the crystalline API.  An example of this is given here.  Crystalline API compounds often have much longer 1H T's than the amorphous excipient compounds.  One can modify the simple CPMAS pulse sequence to discriminate against the excipients with short 1H T's by introducing an additional 1H spin locking pulse before the cross polarization during which the transverse 1H magnetization of the excpient decays to zero while that of the API decays to a much smaller extent.  After the 1H spin locking pulse, cross polarization is applied, transferring polarization from the remaining API 1H magnetization to the API 13C.  This modification to the CPMAS experiment is shown in the figure below.
The figure below illustrates this technique applied to generic acetylsalicylic acid (ASA) tablets.
The spectrum in the bottom panel is a 13C CPMAS spectrum of a crushed generic ASA tablet with a 60 second recycle time and a 2 msec contact time.  One can see the nine 13C resonances of the ASA plus the broad excipient signals between 50 ppm and 110 ppm (highlighted in yellow).  The spectrum in the middle panel was acquired under identical conditions with an additional 10 watt, 12 msec 1H spin locking pulse applied prior to cross polarization.  Clearly, the broader signals of the excipients (with short 1H T) are suppressed leaving only the resonances of the ASA.  The top panel is a weighted difference of the two spectra showing only the signals of the excipients.  Although a pharmaceutical example is used here, the technique is applicable generally to any mixture of solids with different 1H T's.