Flow injection analysis with UV detection versus Raman spectroscopy for the quantitative analysis of Remdesivir

The quality and the safety of sterile preparations in hospital centers are essential to ensure patient safety. The development of rapid and efficient analytical methods is required to control final product before use. In this context, the aim of this study was to compare the performance and interchangeability of two spectral analytical methods: the Flow Injection Analysis (FIA) with UV detection and the Raman spectroscopy for the quality control of preparation before use to quantify the Remdesivir as a SARS-COV2 drug. A quantitative study of remdesivir was performed using clinically relevant concentration range from 0.25 to 1.625 mg.mL-1 in 0,9% NaCl solutions. Samples were analyzed by FIA-UV at 245 nm and by a handheld Raman spectroscopy equipped with a laser at785 nm. Quantitative models were developed using a calibration set (n = 45 samples) and optimized using a validation set (n = 27). An external validation test set (n = 58) was used to compare the two methods and validate the interchangeability by a Bland-Altman plot. Partial least square regression was used to analyse Raman spectra, while univariate analysis was performed at 245 nm for FIA-UV. All the data were analysed with Rstudio software. Based on the calculate accuracy profile, the linearity range and the low limit of quantification (LLOQ) were determined.
As a result, Raman spectra were pretreated by ALS-SG before quantitative analysis. The regression coefficient (r2) was 0.998 and the prediction error for the validation test set was 0.031 mg.mL-1. The calculated LLOQ was 0.25 mg.mL-1 and the validated linearity range was between 0.25 and 1.625 mg.mL-1. For the FIA-UV method, the r2 was 0.989 with a LLOQ at 0.37 mg.mL-1. The linearity range was therefore between 0.37 and 1.625 mg.mL-1. For the Bland-Altman plot, the studied concentration were 0.4 mg.mL-1 and 0.8 mg.mL-1 which were the therapeutic concentration. For both method, the relative error of patient sample were in the interval [-15% ; +15%], which are the acceptable limit in the routine. Finally, the bland Altman plot confirmed the interchangeability of the two methods and the potential of Raman spectroscopy to control Remdesivir during clinical preparation in hospital.

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