Rapid Quantification of Pharmaceuticals via ¹H Solid-State NMR Spectroscopy

Area of Science:

• Analytical Chemistry
• Materials Science
• Pharmaceutical Sciences

Background:

• Physicochemical properties of active pharmaceutical ingredients (APIs) are influenced by their solid-state forms, necessitating accurate characterization for drug product performance.
• Solid-state nuclear magnetic resonance (SSNMR) spectroscopy is selective for API quantification, but traditional methods can be time-consuming.
• While 1H SSNMR enhances sensitivity, low spectral resolution poses challenges for accurate quantification.

Purpose of the Study:

• To introduce a novel 1H SSNMR method, CRAMPS-MAR, for rapid and accurate quantification of APIs.
• To demonstrate the capability of CRAMPS-MAR in achieving high spectral resolution and ease of data analysis for complex APIs.
• To compare the performance of CRAMPS-MAR against existing quantification techniques.

Main Methods:

• Development of CRAMPS-MAR, a technique combining combined rotation and multiple-pulse spectroscopy (CRAMPS) with mixture analysis using references (MAR).
• Application of CRAMPS-MAR using various API species as model systems.
• Comparison with standard quantification approaches, including fast magic angle spinning (MAS) with peak integration and conventional ultra-fast MAS methods.

Main Results:

• CRAMPS-MAR provides high 1H spectral resolution using standard equipment, facilitating straightforward data analysis.
• The method achieves a lower quantitation limit compared to standard fast MAS with peak integration.
• CRAMPS-MAR demonstrates robustness in scenarios challenging for conventional ultra-fast MAS techniques.

Conclusions:

• CRAMPS-MAR offers a significant advancement in rapid API quantification via 1H SSNMR.
• The technique provides a viable alternative for analytical research, overcoming limitations of current methods.
• This method enhances the ability to characterize and quantify APIs, crucial for pharmaceutical development.