Artificial neural networks modeling in ultra performance liquid chromatography method optimization of mycophenolate mofetil and its degradation products

The study of experimental design in conjunction with artificial neural networks for optimization of isocratic ultra performance liquid chromatography method for separation of mycophenolate mofetil and its degradation products has been reported. Experimental design showed to be suitable for selection of experimental scheme, while Kennard-Stone algorithm was used for selection of training data set. The input variables were column temperature and composition of mobile phase including percentage of acetonitrile, concentration of ammonium acetate in buffer, and its pH value. The retention factor of the most retentive component and selectivity factors were used as the dependent variables (outputs). In this way, artificial neural network has been applied as a predictable tool in solving a method optimization problem using small number of experiments. Network architecture and training parameters were optimized to the lowest root-mean-square error values, and the network with 5-4-4-4 topology has been selected as the most predictable one. Predicted data were in good agreement with experimental data, and regression statistics confirmed good ability of trained network to predict compounds retention. The optimal chromatographic conditions included column temperature of 40 degrees C, flow rate of 700 mu l min(-1), 26% of acetonitrile and 9 mM ammonium acetate in mobile phase, and buffer pH of 5.87. The chromatographic analysis has been achieved within 5.2 min. The validation of the proposed method was also performed considering selectivity, linearity, accuracy, precision, limit of detection, and limit of quantification, and the results indicated that the method fulfilled all required criteria. The method was successfully applied to the analysis of commercial dosage form. Copyrigh

Field-assisted paper spray mass spectrometry for therapeutic drug monitoring: 1. the case of imatinib in plasma

The field-assisted paper spray (FAPS) \u2013 mass spectrometric method has been employed to quantify the imatinib (IMT) plasma levels in treated patients. The quantitative measurements have been performed on the collisionally generated fragment at m/z 394 of the protonated molecules of IMT and deuterated IMT (d3-IMT), used as internal standard. The FAPS-tandem mass spectrometry (MS/MS) method exhibits some limitations, because of the high number of operative parameters that need to be carefully controlled. For this aim, papers of different geometry, thickness, and porosity were tested. To obtain a more focalized and intense electrical field, a stainless steel needle was mounted axially and placed at 4 kV voltage. The variability observed in the measurements was ascribed either to the inter-individual variability (e.g. the concomitant presence of other compounds such as proteins, lipids, drugs and/or salts in the plasma of different patients) or to the uncontrollable variables in the instrumental setup (e.g. sample deposition, changes in paper spray conditions). Furthermore, the manual sample deposition and solvent dripping strongly affects the measure reproducibility. Despite this, it is interesting to observe that, once applied in blind on 24 real plasma samples, FAPS-MS/MS led to results analogous to those obtained by the well-consolidated liquid chromatography-MS/MS, even if the mean coefficient of variation % (CV%) values of 20.4% and 2.6% were observed for the two methods, respectively. In conclusion, despite CV values are relatively high, it is worth noting that the FAPS-MS/MS method is much more straightforward, rapid and economical than the liquid chromatography-MS/MS one, and it appears therefore very promising for applications where a high precision is not always a required task, as e.g. in some cases of therapeutic drug monitoring