The silica surface of immobilized artificial membranes containing phosphatidylcholine (IAM.PC) has approximately two aminopropyl groups per immobilized phosphatidylcholine molecule. Primary amines near the silica subsurface adsorb biomolecules and also decrease the chemical stability of IAM.PC surfaces. Consequently, subsurface amines were end-capped by several methods including silylating reagents, acetyl analogues, glycidol, methyl glycolate, short-chain anhydrides (3-6 carbons/anhydride chain), and long-chain anhydrides (10-12 carbons/anhydride chain). All end-capping reactions resulted in loss of the initially immobilized phosphatidylcholine molecule. However, the amount of PC loss during end capping was very low (for alkyl anhydride end-capping reactions) to very high (for silylation end-capping reactions). After end capping, IAM.PC showed increased chemical stability compared to non end-capped IAM.PC surfaces. The chemical stability of IAM packing material was monitored by phospholipid leaching from IAM surfaces exposed to organic and aqueous solvents using thin-layer chromatography, 1H NMR spectroscopy, infrared spectroscopy, and mass spectrometry. IAM.PC packing material end capped with long-chain anhydrides exhibited the greatest chemical stability, i.e., little or no detectable phospholipid leaching when challenged with aqueous and/or organic solvents. The chromatography of acidic and basic compounds on end-capped and non-end-capped IAM.PC surfaces was studied. Compared to non-end-capped IAM.PC HPLC columns, the chromatographic retention times of acidic compounds (deoxynucleotides) decreased after end capping. In contrast, the retention times of basic compounds (amphetamine analogues) increased on end-capped IAM.PC HPLC columns relative to non-end-capped IAM.PC HPLC columns. This indicates that these solutes have access to the silica subsurface amines during chromatography.