In palliative care, continuous subcutaneous infusion (CSCI) is common practice for drug administration when oral application of drugs is not feasible or not reliable anymore. However, use of CSCI is limited to chemical stability of drugs and their combination in carrier solution. To determine the stability of different mixtures of commonly used drugs in palliative care, a multi-analyte UHPLC-DAD method controlled by an internal standard was successfully developed. The method was validated in terms of specificity, accuracy, precision, and linearity across the calibration range. Seven analytes could be separated within 10 min by C18-reversed phase chromatography. The method was successfully applied to close gaps in stability data and complete missing data for decision makers in health care units. Our results indicated the stability of binary mixtures and one ternary mixture in 0.9% saline and 5% glucose as carrier solutions. The obtained data will support pharmacists in palliative care for the preparation of parenteral drug solutions in the future.
The efficient syntheses of 5-(2-hydroxyethyl)- and 5-(3-hydroxypropyl)-substituted pyrimidine derivatives bearing 2,3-dihydroxypropyl, acyclovir-, ganciclovir- and penciclovir-like side chains are reported. A synthetic approach that included the alkylation of an N-anionic-5-substituted pyrimidine intermediate (method A) provided the target acyclonucleosides in significantly higher overall yields in comparison to those obtained by method B using sylilation reaction. The phosphorylation assays of novel compounds as potential substrates for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK) showed that solely pyrimidine 5-substituted acyclonucleosides with a penciclovir-like side chain acted as a fraudulent substrates of HSV-1 TK. Moreover, the uracil derivative with penciclovir-like side chain with less bulky 2-hydroxyethyl substituent at C-5 proved to be a better substrate than the corresponding one with a 3-hydroxypropyl substituent. Therefore, this acyclonucleoside was selected as a lead compound for the development of a positron emission tomography HSV-1 TK activity imaging agent.
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