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

Abstract

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 × (2) × 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.

On the Spectral Quality of Time-Resolved CMOS SPAD-Based Raman Spectroscopy With High Fluorescence Backgrounds

“…Although that this study showed that there is still a lot of work to do to harness the full potential of time-resolved CMOS SPAD line sensors for Raman spectroscopy, it should be noted that the CMOS SPAD-based Raman spectroscopy has already shown its potential in various conventionally challenging applications, such as Raman analyses through single optical fibers, analysis of fluorescent pharmaceuticals, quantification of pickle liquor and chemical imaging of human teeth and rare earth element bearing rocks [16], [29]- [32]. The field of CMOS SPAD-based Raman spectroscopy is still relatively young (the first conference paper about the topic was published less than a decade ago [11]) but the developments made in the sensor architectures and performances promise a bright future for the time-resolved CMOS SPAD-based Raman spectroscopy.…”

Chemical analysis using 3D printed glass microfluidics

“…4d-i) has the further advantage that Raman spectra can be efficiently obtained in the presence of uorescence and other photoluminescent phenomena. 52,53 This is achieved through temporal rejection of the uorescence signal, which, unlike the near instantaneous Raman signal, typically occurs on the order of nanoseconds (or even longer). 54 This expands the range of possible glass materials (e.g.…”

Quantification of Synthetic Nonmetallic Inclusion Multiphase Mixtures from a CaO–Al2O3–MgO–CaS System Using Raman Spectroscopy

“…This type of Raman spectroscopy was designed for effective fluorescence suppression compared with the use of conventional Raman spectroscopy. [ 29 ]…”