Time-Gated Raman Spectroscopy for Quantitative Determination of Solid-State Forms of Fluorescent Pharmaceuticals

6533b858fe1ef96bd12b643a

RESEARCH PRODUCT

Time-Gated Raman Spectroscopy for Quantitative Determination of Solid-State Forms of Fluorescent Pharmaceuticals

Jukka Heikkonen Tiina Lipiäinen Jenni Pessi Juha Koivistoinen Tapio Pahikkala Clare J. Strachan Jouko Yliruusi Anne Juppo Lauri T. Kurki Parisa Movahedi Mari Tenhunen

subject

Time Factors spektroskopia 116 Chemical sciences Analytical chemistry 02 engineering and technology Spectrum Analysis Raman 01 natural sciences Signal Analytical Chemistry symbols.namesake Time domain Least-Squares Analysis ta116 DETECTOR Fluorescent Dyes SUPPRESSION ta113 ta114 Chemistry 010401 analytical chemistry Detector MIXTURES SENSOR PIROXICAM RESONANCE 021001 nanoscience & nanotechnology RAY-POWDER DIFFRACTION Fluorescence 0104 chemical sciences SPAD Pharmaceutical Preparations PHOTON AVALANCHE-DIODE Temporal resolution Raman spectroscopy symbols CRYSTALLIZATION 0210 nano-technology Raman spectroscopy Ternary operation Quantitative analysis (chemistry)

description

Raman spectroscopy is widely used for quantitative pharmaceutical analysis, but a common obstacle to its use is sample fluorescence masking the Raman signal. Time-gating provides an instrument-based method for rejecting fluorescence through temporal resolution of the spectral signal and allows Raman spectra of fluorescent materials to be obtained. An additional practical advantage is that analysis is possible in ambient lighting. This study assesses the efficacy of time-gated Raman spectroscopy for the quantitative measurement of fluorescent pharmaceuticals. Time-gated Raman spectroscopy with a 128 X (2) X 4 CMOS SPAD detector was applied for quantitative analysis of ternary mixtures of solid-state forms of the model drug, piroxicam (PRX). Partial least-squares (PLS) regression allowed quantification, with Raman-active time domain selection (based on visual inspection) improving performance. Model performance was further improved by using kernel-based regularized least-squares (RLS) regression with greedy feature selection in which the data use in both the Raman shift and time dimensions was statistically optimized. Overall, time-gated Raman spectroscopy, especially with optimized data analysis in both the spectral and time dimensions, shows potential for sensitive and relatively routine quantitative analysis of photoluminescent pharmaceuticals during drug development and manufacturing. Peer reviewed

year	journal	country	edition	language
2018-01-01

10.1021/acs.analchem.8b00298 http://hdl.handle.net/10138/256022