“…There are several publications establishing the usefulness of the IAM MB/PB technology to model in vivo drug distribution, such as the volume of distribution model [42], unbound volume of distribution model [43][44] and how they can be used to screen compounds in early drug discovery [45]. It was found that strong IAM MB (CHI IAM > 50) can be related to phospholipidosis [46][47], as well as high volume of distribution and tissue partitioning [43].…”
“…There are several publications establishing the usefulness of the IAM MB/PB technology to model in vivo drug distribution, such as the volume of distribution model [42], unbound volume of distribution model [43][44] and how they can be used to screen compounds in early drug discovery [45]. It was found that strong IAM MB (CHI IAM > 50) can be related to phospholipidosis [46][47], as well as high volume of distribution and tissue partitioning [43].…”
“…All monolithic columns reported in this study were fabricated in our lab [11,12,[15][16][17][18], and their functional groups can be seen in Fig. S2.…”
Section: Preparation Of Monolithic Columnsmentioning
confidence: 99%
“…It has been reported that both hydrophobic and electrostatic interactions may contribute to the retention of charged analytes (such as charged drugs, intact proteins, etc.) on phospholipid-functionalized monoliths [9,11,12,18]. Therefore, several single phospholipid or mixed phospholipid-functionalized monoliths, including the poly (MDPC-co-EDMA), poly (MDPS-co-EDMA), poly (MDPC 90 PS 10 -co-EDMA) and poly (MDPC 60 PA 40 -co-EDMA) monoliths, were selected for the separation of the triad of peptides.…”
Section: Comparison Of Separation Selectivity Of Different Monolithsmentioning
confidence: 99%
“…Recently, a series of phospholipid-functionalized monoliths were developed for studying drug-membrane interactions [9][10][11] and predicting the phospholipidosis-inducing risk of drug candidates [12]. Moreover, these bio-membrane mimicking monoliths exhibited good separation ability for a wide range of compounds including small molecules, peptides, and intact proteins [9,11,13,14] owing to their mixed-mode interactions. Therefore, it is of interest to investigate the applicability of these phospholipidfunctionalized monoliths for the separation of deamidation related residues of mAbs.…”
“…Phoshorylcholine monolith allowed a separation of small hydrophilic peptides, which was not observed on a sulfobetaine‐based monolithic column , which might be probably attributed to a better biocompatibility of choline functionality. Indeed, phosphatidylcholine modified monolithic stationary phases were successfully used as immobilized artificial membranes . After chain‐end n ‐butyl group is introduced in zwitterionic functional group, higher selectivity and efficiency is achieved when compared to classical phoshorylcholine methacrylate with ethyl end group .…”
In this work, we aimed to prepare a monolithic capillary column that allowed an isocratic separation of ten dopamine precursors and metabolites in a single run. Segments of five zwitterion sulfobetaine polymer monoliths have been modified by zwitterion phoshorylcholine by using an ultraviolet‐initiated two‐step photografting. Columns with 0, 33, 50, 66, and 100% of modified length were prepared. Effect of length of the modified segment and mobile phase composition has been tested. All columns provided dual‐retention mechanism with reversed‐phase retention in highly aqueous mobile phase and hydrophilic interaction mechanism in highly organic mobile phase. The retention mechanism was controlled by the composition of the mobile phase and has been described by a three‐parameter model. We have used regression parameters to characterize the retention of analyzed compounds and to study individual pathways of dopamine metabolism. Comprehensive optimization of mobile phase composition allowed to find an optimal composition of the mobile phase and stationary phase surface chemistry arrangement to achieve desired separation. Optimized columns provided an isocratic separation of all tested compounds in less than nine min.
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