Background Patient-specific preparations have become a central therapy concept in oncological treatment. The highly potent cytostatic agents are characterised by a narrow therapeutic range. Therefore, exact dosage is important, as lower amounts reduce the effectiveness and higher doses increase the risk of severe side effects. Compound confusion can even result in fatal consequences. Missing dependent and independent controls regarding concentration and identity pose a risk for patient safety.
Purpose We developed a concept for a two-stage quality control of the infusion solutions. Drug identity and concentration can be checked onsite after preparation using a combined UV- and Raman spectrometer (UV-Raman). This is complemented by an independent method using liquid chromatography coupled to UV detection (HPLC-UV).
Material and methods Methods for the analysis of seven cytostatic drugs and two monoclonal antibodies were developed and validated on an i-QCRx UV-Raman system (B and W Tek Europe GmbH, Lübeck, Germany) and on an Agilent 1200 series HPLC-UV system (Agilent Technologies, Waldbronn, Germany). Sample transport and preparation were evaluated to ensure valid results. In a pilot study we analysed samples from different pharmacies in both systems.
Results Method development and validation were successful for the investigated compounds in both systems. HPLC-UV is more sensitive than UV-Raman. However, due to the content of the preparations, real samples had to be diluted before applying HPLC-UV analysis. Sensitivity of the UV-Raman spectrometer fits to the required concentration range without further dilution. All methods showed reproducible results, UV-Raman varied by 0.44% in a repeated analysis (n=3) of 5-fluorouracil, while HPLC-UV varied by 0.14%. Results of the investigated samples were also equivalent. In a sample containing paclitaxel with a target concentration of 0.72 mg/mL we determined 0.73 mg/mL (101%) using UV-Raman and 0.69 mg/mL (96%) using HPLC-UV, for example.
Conclusion UV-Raman and HPLC-UV are suitable for determining the content of patient-individual preparations, both with individual assets and drawbacks. The study showed that the two-stage control concept is appropriate to ensure a high-quality level for patient-individual preparations.
References and/or acknowledgements No conflict of interest.