Analytical Method Development Using Quantum Laser Cascade Spectroscopy with Diffuse and Attenuated Total Reflectance for Determining Low Concentrations of Active Pharmaceutical Ingredients.

Abstract

Quantum Cascade Laser Spectroscopy (QCLS) will quantify acetaminophen as an active pharmaceutical ingredient in different low concentrations formulations in tablet presentation. Tablets contain acetaminophen in nine blends ranging from 0.0% to 3.0% w/w, with mannitol, croscarmellose, cellulose, and magnesium stearate, as excipients. The tablets were analyzed in non-contact mode by mid-infrared attenuated total reflectance and diffuse reflectance backscattering. Measurements were conducted covering the spectral range 770-1890 cm^-1. Calibrations were generated by applying multivariate analysis using principal component analysis. The high power of the quantum cascade laser-based spectroscopic system attached to attenuated total reflectance and diffuse reflectance backscattering resulted in the design of discrimination methodologies for pharmaceutical applications with acetaminophen as an active pharmaceutical ingredient in the formulation. The main conclusion is that attenuated total reflectance is better for other analyses. For tablet analysis using mid-infrared quantum cascade lasers, diffuse reflectance backscattering is more accurate for predicting the API content. QCLS is gaining even more acceptance as a valuable tool in Process Analytical Technology.