Use of surface-enhanced transmission Raman spectroscopy for quantitative impurity analysis in a complex matrix
A study has demonstrated that surface enhanced Raman spectroscopy in transmission mode effectively detects 4-aminophenol impurities within a complex matrix.
- byBevin Likuyani
- 01 Oct, 2024
- 2 Mins
The dynamic world of pharmaceuticals constantly explores new analytical approaches for quality control and assurance.
A recent study published in the Journal of Pharmaceutical and Biomedical Analysis showed that an impurity in a complex matrix can be determined using surface enhanced transmission Raman spectroscopy (SETRS).
Unveiling new possibilities for quantitative analysis applications.
The study aimed to assess the suitability of using SETRS for the quantitative determination of 4-aminophenol (4-AP), a degradation impurity of paracetamol known to be nephrotoxic.
As it stands, the United States Pharmacopeia (USP) recommends the use of liquid chromatography for this test; however, Julie Horne and her co-authors sought to explore a spectroscopic technique, SETRS, known to be more time-efficient.
According to the paper, at the time of publishing, use of surface enhanced Raman scattering (SERS) through transmission detection had not been extensively explored elsewhere in this kind of analysis.
It however, acknowledges that use of a backscattering detection had been “successfully developed” with SERS for the quantitative determination of 4-AP in different studies.
Notably, total error risk-based methodology was used to evaluate SETRS analytical performances for both univariate and multivariate data analysis.
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The quantification of 4-AP was performed in a pharmaceutical formulation that included paracetamol and excipients.
The primary challenge in this context was ensuring the selective SETRS detection of 4-AP, despite the complex matrix having a high concentration of the active drug and excipients.
In the study, the target concentration for 4-AP was set at a maximum of 15 µg/mL in a 100 mL analyzed solution, aligning with USP recommendations of 0.15% (w/w) as the highest tolerable concentration in a pharmaceutical formulation.
Method specificity of SETRS in detecting the 4-AP impurity was ascertained through comparison of 5 samples: a matrix (high concentration of paracetamol and excipients), 3 samples of matrix containing varying concentrations of 4-AP, and a blank containing colloidal silver nanoparticles with an aggregating agent.
The resulting SETRS spectra exhibited distinct bands, with the most prominent band corresponding to the highest concentration of 4-AP, confirming the method's specificity.
In addition, data showed that while a smaller collection optic did not significantly affect signal variability, it did enable more signal amplification.
Comparing the SETRS variability to the backscattering detection mode yielded results that were similar and suggested a tendency towards a smaller relative standard deviation for the transmission mode.
Two methods of calibration were compared: the multivariate method, which was based on a partial least-squares regression (PLSR) model, and the univariate method, which was based on a quadratic regression model of the 580 cm−1 band specific of the 4-AP.
Both methods showed acceptable quantitative performance with respect to bias, repeatability, and intermediate accuracy.
This study opens up new possibilities for quantitative applications by demonstrating that SETRS may be utilized to identify an impurity in complicated matries.
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Bevin Likuyani
Bevin Likuyani is a pharmacist with a Master of Pharmacy in Pharmacoepidemiology and Pharmacovigilance and an MBA from the School of Business, University of Nairobi. He is also a Certified Supply Chain Professional (CSCP) from the American (Association of Supply Chain Management).