Pharmaceutical analysis in solids using front face fluorescence spectroscopy and multivariate calibration with matrix...

Area of Science:

• Analytical Chemistry
• Pharmaceutical Analysis
• Spectroscopy

Background:

• Front face fluorescence spectroscopy (FFS) of solids is sensitive to matrix effects caused by varying excipients in pharmaceutical preparations.
• Excipient variations can lead to spectral displacement, altered fluorescence intensity, and modified band profiles, complicating quantitative analysis.
• Accurate quantification of active pharmaceutical ingredients (APIs) like acetylsalicylic acid (ASA), paracetamol, and caffeine is crucial for drug quality control.

Purpose of the Study:

• To apply piecewise direct standardization (PDS) for effective matrix correction in FFS of solid pharmaceutical mixtures.
• To develop a robust standardization strategy to convert excitation-emission matrices (EEMs) for accurate API quantification.
• To validate the method for simultaneous determination of ASA, paracetamol, and caffeine in the presence of diverse excipients.

Main Methods:

• Utilized front face fluorescence spectroscopy (FFS) to acquire excitation-emission matrices (EEMs) over specified wavelength ranges (Ex: 265-405 nm, Em: 300-480 nm).
• Implemented piecewise direct standardization (PDS) as a matrix correction technique to normalize spectral variations.
• Employed unfolded partial least squares (U-PLS) for quantitative analysis of the standardized EEMs.

Main Results:

• PDS effectively corrected spectral variations caused by different excipients and their ratios.
• U-PLS analysis of standardized EEMs yielded excellent quantitative results for ASA, paracetamol, and caffeine.
• Root mean square error of prediction (RMSEP) values were 8.2 mg/g (ASA), 10.9 mg/g (paracetamol), and 2.7 mg/g (caffeine), with relative errors below 5% for all analytes.

Conclusions:

• Piecewise direct standardization (PDS) is a highly effective strategy for matrix correction in front face fluorescence spectroscopy of solid pharmaceutical formulations.
• The developed method enables accurate and reliable quantification of multiple APIs (acetylsalicylic acid, paracetamol, caffeine) despite significant excipient variability.
• This approach offers a robust solution for quality control and analysis of complex pharmaceutical mixtures using fluorescence spectroscopy.