Validation of18F-DOPA quality control using UPLC®-MSSchepers, M., Maas, B., Bannink, A., Boersma, H. H., Zijlma, R., De Vries, E. F. J., Elsinga, P. H. & Luurtsema, G., 1-May-2013, In : JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS. 56, p. 483 1 p.
Research output: Contribution to journal › Meeting Abstract › Academic
Objectives: 6-[18F]Fluoro-L-DOPA (FDOPA) is used to study the presynaptic dopamine synthesis in vivo using PET . Major indications for this tracer are determination of the disease stage in Parkinson as well as detection of various neuroendocrine tumors and their metastases. Prior to set up a Good Manufacturing Practice (GMP) compliant production, the quality control of FDOPA needs to be validated. The radiopharmaceutical needs to meet the specification as described in the European Pharmacopoeia 7.0 Methods: An Ultra Performance Liquid Chromatography UPLC® with an online radioactivity detector was used to measure the concentrations of FDOPA and impurities. For identification of the parent compound and its impurities an UPLC® coupled to a Xevo® G2 QTof mass spectrometer was used. The different components were separated on an Waters ACQUITY UPLC® HSS T3 1.8 μm, 3.0 x 50 mm analytical column. The eluent is 0.05 M sodium dihydrogen phosphate buffer pH 2.5 with an isocratic flow of 0.8 ml/min. Total run time is 3 minutes. Several calibration samples of FDOPA were measured to determine linearity, reproducibility, stability, LOQ, LOD and the resolution. Furthermore the linearity of the Berthold flowstar LB 513 online radioactivity detector was measured. For identification of the parent compound and impurities, a sample was taken directly after the [18F]FDOPA synthesis. The measurements with the mass spectrometer were performed in negative resolution mode with an electrospray source in a range from 50 to 1200 Da. The masses of interest of FDOPA, DOPA, 6-hydroxy- DOPA and FDOPA-quinone (see fig. 1) are respectively 214.0516, 196.0610, 212.0559 and 212.0359 Da. (Figure presented) Results: The analyses using UPLC® in combination with online radioactivity detector were validated. FDOPA and side products DOPA and FDOPA-quinone were detected and identified in the production batches. The concentrations were 1040, 0.1 and 61.5 μg/mL (n = 19), respectively. The samples were measured over a period time of 9 weeks after production and showed a clear increase in the concentration of FDOPA- quinone over time. The DOPA concentration decreasing over this period. In all the samples the concentration of 6-hydroxy- DOPA was below the detection limit and therefore it was not possible to identify this side product with UPLC® -MS. The main impurity was FDOPA-quinone, which is not described in the European Pharmacopoeia 7.0. Conclusions: The quality control of FDOPA using UPLC® -RA was validated for GMP productions. The UPLC® method is reproducible and the retention times of the desired compounds are very short. This is of advantage for rapid releasing the production batch for human application.
|Number of pages||1|
|Journal||JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS|
|Publication status||Published - 1-May-2013|
- fluorine 18, radiopharmaceutical agent, DOPA, quinone derivative, tracer, sodium dihydrogen phosphate, water, guanosine phosphate, quality control, ultra performance liquid chromatography, radioactivity, mass spectrometer, parent, human, medical literature, reproducibility, good manufacturing practice, dopamine metabolism, pH, synthesis, metastasis, neuroendocrine tumor, limit of detection, electrospray