Real-time simultaneous detection of microbial contamination and determination of an ultra low-content active pharmaceutical ingredient in tazarotene gel by near-infrared spectroscopy

Abstract

This paper proposes and proves a real-time and non-destructive strategy for sensitive and simultaneous detection of microbial contamination and determination of an ultra low-content active pharmaceutical ingredient in tazarotene gel by near-infrared (NIR) spectroscopy. In this experiment, 88 samples of tazarotene gel (0.41–0.65 mg g⁻¹ of tazarotene) were prepared using the standard addition method. Among them, 47 samples were inoculated with 50 μl of different concentrations of Escherichia coli (E. coli) DH5a in Luria–Bertani (LB) broth to give 1–4 log CFU g⁻¹ of E. coli DH5a in the gel, 6 samples with 50 μl of LB broth, and 35 samples with nothing. Based on the gel NIR transflectance spectra, E. coli DH5a in the gel was detected by the counter propagation artificial neural network (CP-ANN) model with a classification accuracy of 100.0%, while tazarotene in the gel was simultaneously determined by the partial least squares regression (PLS) model with a root mean square error of cross-validation of 0.0232 mg g⁻¹. Furthermore, 9 samples of real tazarotene gel were used to verify the practicality of the established NIR spectroscopy. The developed NIR strategy can be used to correctly and quickly release the pharmaceutical gels, required for sensitive and simultaneous control of microbial contamination and the active pharmaceutical ingredient (API) content, to the next stage.