6ER-001 High versus low dose of ursodeoxycholic acid for the management of intrahepatic cholestasis of pregnancy: a cohort retrospective study of maternal and neonatal outcomes

Abstract

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 UVand 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 highquality level for patient-individual preparations.