Development of acidic phospholipid containing immobilized artificial membrane column to predict drug-induced phospholipidosis potency.

Drug-induced phospholipidosis (DIPLD) represents a big concern for both regulatory authorities and pharmaceutical companies in drug discovery. Many researches pointed out that the negatively charged intralysosomal lipids play an important role in the formation of DIPLD. To better mimic this negatively charged lipid surface, a novel immobilized artificial membrane (IAM) column was prepared via in situ copolymerization of 12-methacryloyl n-dodecylphosphocholine (MDPC) and 12-methacryloyl n-dodecylphosphoric acid (MDPA). By introducing MDPA, the surface of the resulting monolithic column can be maintained negatively charged over a broad pH range. Scanning electron microscopy, elemental analysis and nano-HPLC experiments were carried out to characterize the physicochemical properties and chromatographic performance of the obtained monolithic IAM column. The results of ζ-potential and retention mechanism studies indicate that both hydrophobic and electrostatic interactions contribute greatly to the retention of cation analytes owing to the existence of the negatively charged MDPA under acidic conditions. To better assess the DIPLD potency of drug, the molar ratio between MDPC and MDPA in the monolithic column was carefully optimized. The results show that the poly(MDPC

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Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.