Application of Raman Spectroscopy to the analysis of complex Therapeutic Objects: Analytical Quality Control and Release Testing of portable infusion devices with a polyisoprene membrane charged with 5FU

Introduction
Analytical Quality Control and Release Testing (AQCRT) of Therapeutic Objects (TO) is becoming widely adopted as it plays a role in making the medication circuit safer. Now, some commonly used TOs have a design and/or volume that is hardly compatible with the implementation of AQCRT. Portable infusion devices belong to this category: are they eligible for AQCRT by Raman Spectroscopy (RS)?

Objective
To evaluate the performance and practicality of RS applied to AQCRT of portable infusion devices with a polyisoprene (PI) membrane charged with a 5FU solution.

Equipment and methods
Quantification of the 5FU is conducted in conditions representative of the usual therapeutic protocols by CLHP-UV and RS. Dilution series (n = 9) and CQs (n = 4) prepared with 0.9% NaCl and 5% glucose cover an interval of concentrations of between 1.5 to 50 mg/ml. The quantification model for 5FU was validated vs complex TOs, i.e. BAXTER SV2Infusor® infusion devices.

Results
Analysis in spectral dissociation reveals a differentiating, intense and specific band quantification of the 5FU (777-747 cm-1). The dilution series are linear in the retained interval (r2>0.99). The technique shows satisfactory repeatability (CVs ≤ 10 %) and accuracy of between 95 and 105 %. There is a strong correlation between the concentrations of 5FU measured via RS vs CLHP (p < 0.00001; n = 36 - Spearman test and rs Kendall).

Discussion – conclusion
CQAL by RS of nevertheless complex TOs such as infusion devices with PI membrane again appear to be a choice technical option. We confirm the relevance of RS application and its multiple advantages including:

1. respect for the integrity of the formed TO,
2. removal of any risk of operator exposure,
3. preservation of the environment (no consumables),
4. simplicity of analysis,
5. practically no maintenance needed.

In addition, the present study considerably widens the field of application for RS to AQCRT of TOs with a broad spectrum of uses and complex geometry for which no other analytical solution had hitherto provided a response.