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Title: Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions

Abstract

Second harmonic generation (SHG) was integrated with Raman spectroscopy for the analysis of pharmaceutical materials. Particulate formulations of clopidogrel bisulfate were prepared in two crystal forms (Form I and Form II). Image analysis approaches enable automated identification of particles by bright field imaging, followed by classification by SHG. Quantitative SHG microscopy enabled discrimination of crystal form on a per particle basis with 99.95% confidence in a total measurement time of ~10 ms per particle. Complementary measurements by Raman and synchrotron XRD are in excellent agreement with the classifications made by SHG, with measurement times of ~1 min and several seconds per particle, respectively. Coupling these capabilities with at-line monitoring may enable real-time feedback for reaction monitoring during pharmaceutical production to favor the more bioavailable but metastable Form I with limits of detection in the ppm regime.

Authors:
; ; ; ; ; ; ; ORCiD logo; ; ; ; ORCiD logo
Publication Date:
Research Org.:
Argonne National Lab. (ANL), Argonne, IL (United States). Advanced Photon Source (APS)
Sponsoring Org.:
National Science Foundation (NSF)
OSTI Identifier:
1373787
Resource Type:
Journal Article
Resource Relation:
Journal Name: Analytical Chemistry; Journal Volume: 89; Journal Issue: 11
Country of Publication:
United States
Language:
ENGLISH
Subject:
37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY

Citation Formats

Chowdhury, Azhad U., Ye, Dong Hye, Song, Zhengtian, Zhang, Shijie, Hedderich, Hartmut G., Mallick, Babita, Thirunahari, Satyanarayana, Ramakrishnan, Srividya, Sengupta, Atanu, Gualtieri, Ellen J., Bouman, Charles A., and Simpson, Garth J. Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions. United States: N. p., 2017. Web. doi:10.1021/acs.analchem.7b00431.
Chowdhury, Azhad U., Ye, Dong Hye, Song, Zhengtian, Zhang, Shijie, Hedderich, Hartmut G., Mallick, Babita, Thirunahari, Satyanarayana, Ramakrishnan, Srividya, Sengupta, Atanu, Gualtieri, Ellen J., Bouman, Charles A., & Simpson, Garth J. Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions. United States. doi:10.1021/acs.analchem.7b00431.
Chowdhury, Azhad U., Ye, Dong Hye, Song, Zhengtian, Zhang, Shijie, Hedderich, Hartmut G., Mallick, Babita, Thirunahari, Satyanarayana, Ramakrishnan, Srividya, Sengupta, Atanu, Gualtieri, Ellen J., Bouman, Charles A., and Simpson, Garth J. Mon . "Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions". United States. doi:10.1021/acs.analchem.7b00431.
@article{osti_1373787,
title = {Second Harmonic Generation Guided Raman Spectroscopy for Sensitive Detection of Polymorph Transitions},
author = {Chowdhury, Azhad U. and Ye, Dong Hye and Song, Zhengtian and Zhang, Shijie and Hedderich, Hartmut G. and Mallick, Babita and Thirunahari, Satyanarayana and Ramakrishnan, Srividya and Sengupta, Atanu and Gualtieri, Ellen J. and Bouman, Charles A. and Simpson, Garth J.},
abstractNote = {Second harmonic generation (SHG) was integrated with Raman spectroscopy for the analysis of pharmaceutical materials. Particulate formulations of clopidogrel bisulfate were prepared in two crystal forms (Form I and Form II). Image analysis approaches enable automated identification of particles by bright field imaging, followed by classification by SHG. Quantitative SHG microscopy enabled discrimination of crystal form on a per particle basis with 99.95% confidence in a total measurement time of ~10 ms per particle. Complementary measurements by Raman and synchrotron XRD are in excellent agreement with the classifications made by SHG, with measurement times of ~1 min and several seconds per particle, respectively. Coupling these capabilities with at-line monitoring may enable real-time feedback for reaction monitoring during pharmaceutical production to favor the more bioavailable but metastable Form I with limits of detection in the ppm regime.},
doi = {10.1021/acs.analchem.7b00431},
journal = {Analytical Chemistry},
number = 11,
volume = 89,
place = {United States},
year = {Mon May 08 00:00:00 EDT 2017},
month = {Mon May 08 00:00:00 EDT 2017}
}