Development of a non-destructive dosage method by Raman spectroscopy, applied to 5-Fluorouracil solutions

B. Dectot, N. Simon, M. Vasseur, B. Décaudin, P. Odou Univ. Lille, CHU Lille, EA 7365 - GRITA - Groupe de Recherche sur les formes Injectables et les Technologies Associées, F-59000 Lille, France

Objective

The current releasing analytical quality control (RAQC) techniques for injectable anticancer drug (IAD) all need a sample to analyse, exposing the staff and the environment to a cytotoxic risk. This work aims to develop a non-invasive dosing method in using the Raman spectroscopy (RS).

Method

Firstly, the optimum conditions of use of the apparatus (QCPrép+, Icône Services) have been defined: height of the laser beam, position and size of the drug container (syringes and plastic bags), drug signal intensity, effect of the solvent (dextrose 5% and NaCl 0.9%).

Secondly, the analytical validation has been performed with 3 series of 5 calibration points (1-14 mg/mL) and 4 validation points (3-12 mg/mL) (repeated 3 times). The prediction model is developed by multilinear regression.

The preparation chosen for this study is Fluorouracil (FU) diluted in 100 mL NaCl injection solution, because of its large prescription.

Dosage results are presented by the percentage of certified preparations using 3 target concentration acceptance levels: ±15, 10 and 5%.

Results

Preliminary tests define an optimal position of the analyzed object. Excluding the 1mL syringe which is too small to get a proper measure, the incidence of the container or solution is insignificant.

For the respective acceptance bias of ±15, 10 and 5%, the percentage of certified preparations are 97.2%, 91.7% and 44.4%. The means ± standard deviation of relative bias for the concentrations of 3, 6, 9 and 12 mg/mL are respectively 2.2±4.8%, 2.3±7.6%, 2.6±4.3% and -3.5±8.1%.

Discussion/Conclusion

This study shows the possibility to dose FU in NaCl bag using RS with acceptance limit of 15%, or even 10%. The plastic bag may present wrinkles causing imprecision. The continuation of the study with other drugs and containers shall conclude about its use as a routine RAQC, enabling to secure the compounding of IAD.

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