New applicable breakthrough of Raman spectroscopy to the verification of the analytical quality of injectable solutions of anthracyclines

Introduction:

The advent of Injectable Production Centres goes hand in hand, as often as possible, with the performance of high performance Analytic Quality Inspection (AQI) of identity, purity and concentration. Raman Spectroscopy (RS) is a vibration analysis technique enabling a direct, non destructive and rapid treatment of numerous chemical species through the primary packaging of Therapeutic Objects (TOs).

Objective:

Evaluation of the performance and practicality of RS for the on-line AQI of 2 major and structurally very similar anthracyclines, namely epirubicin (4 EA - Epirubicin TEVA®) and doxorubicin (ADR).

Material and methods:

the analysis was undertaken using a Raman RXN1 spectrometer (Kaiser Optical system) fitted with a LASER source. The ranges of the 2 isomers (0 to 2 mg/ml), of the 3 QCs and of the TOs (0.5 to 2 mg/ml) were made in syringes (NaCl 0.9 % and G 5 %). The results were compared to those obtained with a CLHP-UV method. The crossed specificity of the spectral signatures was explored.

Results:

4-EA and ADR have characteristic RS spectral profiles, evidencing the good specificity of the technique (differentiating band at 375 cm-1). The quantification band is common (1196 to 1220 cm-1). The ranges are linear within the interval of the concentrations taken (r2>0.99). The technique offers satisfactory fidelity (CV<10 %) and a precision of > 90 %. There is a high correlation between the concentrations measured with RS compared to CLHP (p < 0.001) for the 2 species.

Discussion - conclusion:

RS analysis of therapeutic solutions of 4-EA or ADR is reliable, powerful and much simpler than any other technical option available in AQI. Following on from a previous study devoted to oxazaphosphorines, these new data confirm the high potential of RS in AQI applications related to a wide range of TOs. Among the advantages of the Raman solution, the following must be emphasised:

1. respect of the integrity of the TO as made,
2. absence of risk for operators,
3. preservation of the environment, thanks to the absence of consumables,
4. the simplicity of the analysis, and
5. the « negligible » maintenance required for the equipment.

We confirm the very promising character of the innovative Raman application as a co-factor for ensuring the safety of the drug circuit.