Quantitation of active pharmaceutical ingredient through the packaging using Raman handheld spectrophotometers: A...

Area of Science:

• Analytical Chemistry
• Spectroscopy
• Pharmaceutical Analysis

Background:

• Handheld Raman spectroscopy is rapidly advancing, with improvements targeting fluorescence, sensitivity, and surface analysis limitations.
• While qualitative assessments are established, quantitative analysis of pharmaceutical samples using these devices remains a significant challenge.

Purpose of the Study:

• To compare the quantitative performance of three commercially available handheld Raman spectroscopy devices.
• To evaluate their efficacy in analyzing pharmaceutical ternary mixtures under various conditions.

Main Methods:

• Three handheld Raman spectrometers (785 nm and 830 nm lasers, backscattering, SORS, ORS modes) were tested.
• Ibuprofen-mannitol-microcrystalline cellulose mixtures (24-52% ibuprofen) were analyzed directly through glass vials or within opaque flasks.
• Quantitative models were developed using Partial Least Squares Regression (PLS-R) and validated against FT-NIR spectroscopy using the total error approach and ICH guidelines.

Main Results:

• The study evaluated the quantitative accuracy and precision of different handheld Raman devices.
• Model validation using the total error approach and ICH Q2 (R1) guidelines with ±15% acceptance limits was performed.
• Performance varied between devices and measurement conditions, highlighting the need for careful method development and validation.

Conclusions:

• Handheld Raman spectroscopy demonstrates potential for quantitative pharmaceutical analysis, but performance is device-dependent.
• Rigorous validation using established guidelines is crucial for reliable quantitative results.
• Further research may optimize handheld Raman spectroscopy for routine pharmaceutical quality control.