Karolinska Radiopharmacy, Karolinska University Hospital, Akademiska stråket 1, S-171 64 Stockholm, Sweden Department of Oncology-Pathology, Karolinska Institutet, Akademiska stråket 1, S-171 77 Stockholm, Sweden
Dr. Mohammad Mahdi Moein
Karolinska Radiopharmacy, Karolinska University Hospital, Akademiska stråket 1, S-171 64 Stockholm, Sweden Department of Oncology-Pathology, Karolinska Institutet, Akademiska stråket 1, S-171 77 Stockholm, Sweden
Due to their selectivity and chemical stability, molecularly imprinted polymers have attracted great interest in sample preparation. Imprinted polymers have been applied for the extraction and the enrichment of different sorts of trace analytes in biological and environmental samples before their analysis. Additionally, MIPs are utilized in various sample preparation techniques such as SPE, SPME, SBSE and MEPS. Nevertheless, molecularly imprinted polymers suffer from thermal (stable only up to 150 °C) and mechanical stability issues, improper porosity and poor capacity. The sol-gel methodology as a promising alternative to address these limitations allowing the production of sorbents with controlled porosity and higher surface area. Thus the combination of molecularly imprinted technology and sol-gel technology can create influential materials with high selectivity, high capacity and high thermal stability. This work aims to present an overview of molecularly imprinted sol-gel polymerization methods and their applications in analytical and bioanalytical fields.
By using solid targets in medical cyclotrons, it is possible to produce large amounts of 68GaCl3. Purification of Ga3+ from metal ion impurities is a critical step, as these metals compete with Ga3+ in the complexation with different chelators, which negatively affects the radiolabeling yields. In this work, we significantly lowered the level of iron (Fe) impurities by adding ascorbate in the purification, and the resulting 68GaCl3could be utilized for high-yield radiolabeling of clinically relevant DOTA-based tracers. 68GaCl3 was cyclotron-produced and purified with ascorbate added in the wash solutions through the UTEVA resins. The 68Ga eluate was analyzed for radionuclidic purity (RNP) by gamma spectroscopy, metal content by ICP-MS, and by titrations with the chelators DOTA, NOTA, and HBED. The 68GaCl3eluate was utilized for GMP-radiolabeling of the DOTA-based tracers DOTATOC and FAPI-46 using an automated synthesis module. DOTA chelator titrations gave an apparent molar activity (AMA) of 491 ± 204 GBq/µmol. GMP-compliant syntheses yielded up to 7 GBq/batch [68Ga]Ga-DOTATOC and [68Ga]Ga-FAPI-46 (radiochemical yield, RCY ~ 60%, corresponding to ten times higher compared to generator-based productions). Full quality control (QC) of 68Ga-labelled tracers showed radiochemically pure and stable products at least four hours from end-of-synthesis.
A wooden stick coated with a novel graphene-based nanocomposite (Graphene oxide/polyethylene glycol (GO/PEG)) is introduced and investigated for its efficacy in solid phase microextraction techniques. The GO/PEG-stick was prepared and subsequently applied for the extraction of β-blockers, acebutolol, and metoprolol in human oral fluid samples, which were subsequently detected by liquid chromatography tandem mass spectrometry (LC-MS/MS). Experimental parameters affecting the extraction protocol including sample pH, extraction time, desorption time, appropriate desorption solvent, and salt addition were optimized. Method validation for the detection from oral fluid samples was performed following FDA (Food and Drug Administration) guidelines on bioanalytical method validation. Calibration curves ranging from 5.0 to 2000 nmol L−1 for acebutolol and 25.0 to 2000 nmol L−1 for metoprolol were used. The values for the coefficient of determination (R2) were found to be 0.998 and 0.996 (n = 3) for acebutolol and metoprolol, respectively. The recovery of analytes during extraction was 80.0% for acebutolol and 62.0% for metoprolol, respectively. The limit of detections (LODs) were 1.25, 8.00 nmol L−1 for acebutolol and metoprolol and the lower limit of quantifications (LLOQ) were 5.00 nmol L−1 for acebutolol and 25.0 nmol L−1 for metoprolol. Validation experiments conducted with quality control (QC) samples demonstrated method accuracy between 80.0% to 97.0% for acebutolol and from 95.0% to 109.0% for metoprolol. The inter-day precision for QC samples ranged from 3.6% to 12.9% for acebutolol and 9.5% to 11.3% for metoprolol. Additionally, the GO/PEG-stick was demonstrated to be reusable, with the same stick observed to be viable for more than 10 extractions from oral fluid samples.