Development of a retention prediction model in ion-pair reversed-phase HPLC for nucleoside triphosphates used as mRNA vaccine raw materials.

The International Conference on Harmonization guidelines for quality on pharmaceutical development recommends a systematic development approach including robustness studies which assure performance of manufacturing and analytical method development of drug product. It was demonstrated that the retention prediction model for nucleoside triphosphates (NTPs) on ion-pair reversed-phase HPLC was developed by a highly accurate Kawabe's model which supports the development of robust HPLC methods. As NTPs and its derivatives are typically used for Messenger ribonucleic acid (mRNA) vaccine production, adenosine-5'-triphosphate (ATP), guanosine-5'-triphosphate (GTP), cytidine-5'-triphosphate (CTP), 5-methylcytidine-5'-triphosphate (m-CTP), uridine-5'-triphosphate (UTP), 5-methyluridine-5'-triphosphate (m-UTP), pseudouridine-5'-triphosphate (Ψ-UTP) and N1-methylpseudouridine-5'-triphosphate (mΨ-UTP) were applied for prediction model development.

The development of retention time prediction model using multilinear gradient profiles of seven pharmaceuticals.

The ICH guidance on pharmaceutical development recommends a systematic development approach including robustness studies which assure performance of manufacturing and analytical method development of drug product. The retention model by T. Kawabe et al have an excellent correlation between observed and predicted retention time in various kinds of pharmaceutical compounds during isocratic elution by the multiple regression modeling of solvent strength parameters.

Ternary isocratic mobile phase optimization utilizing resolution Design Space based on retention time and peak width modeling.

An optimization procedure of ternary isocratic mobile phase composition in the HPLC method using a statistical prediction model and visualization technique is described. In this report, two prediction models were first evaluated to obtain reliable prediction results. The retention time prediction model was constructed by modification from past respectable knowledge of retention modeling against ternary solvent strength changes.

A prediction system of oxidation reaction as a solid-state stress condition: applied to a pyrrole-containing pharmaceutical compound.

Stress conditions for predicting oxidative degradation products in solid-state pharmaceutical compounds were investigated. 4-Methyl-2-(3,4-dimethylphenyl)-1-(4-sulfamoylphenyl)pyrrole, Compound A, was used as the model compound for this study and its four main degradation products were due to oxidation, as identified by LC-MS and LC-(1)H NMR. In order to develop a prediction system for the oxidation reaction, solid-state Compound A was stored under moisture-saturated conditions.

A study of the relationship between the chemical structures and the fluorescence quantum yields of coumarins, quinoxalinones and benzoxazinones for the development of sensitive fluorescent derivatization reagents.

To develop new fluorescent derivatization reagents, we investigated the relationship between the chemical structures and the fluorescence quantum yields (phi(f)) of coumarins, quinoxalinones and benzoxadinones. Forty-six compounds were synthesized and their fluorescence spectra were measured in n-hexane, ethyl acetate, methanol and water. The energy levels of these compounds were calculated by combination of the semi-empirical AM1 and INDO/S (CI = all) methods.

A method to evaluate the renin-angiotensin system in rat renal cortex using a microdialysis technique combined with HPLC-fluorescence detection.

A microdialysis (MD) technique, combined with HPLC-fluorescence (FL) detection, was developed for the evaluation of the tissue-specific renin-angiotensin system (RAS) in the rat renal cortex. An MD probe constructed with a hydrophilic hollow fiber dialysis tubing, AN69, showed high recovery (more than 50%) in vitro for all four angiotensins: angiotensin I (Ang I), Ang II, Ang III, and Ang (1-7). Angiotensins, successfully derivatized with m-BS-ABD-F, a water-soluble fluorogenic reagent that has a 2,1,3-benzoxadiazole (benzofurazan) structure, could be simultaneously determined by coupled-column HPLC.