Analysis of tricyclic antidepressants in human plasma using online-restricted access molecularly imprinted solid phase extraction followed by direct mass spectrometry identification/quantification.

The use of a new class of hybrid materials, called restricted access molecularly imprinted polymers (RAMIPs) seems to present a good strategy for the sample preparation of complex matrices, since these materials combine good protein elimination capacity with high degree selectivity. Mass spectrometers (MS) have been successfully used for polar drug identification and quantification. In order to combine the advantages of both RAMIPs and mass spectrometry, we proposed a study that joins these properties in a single system, where we could analyse tricyclic antidepressants from human plasma, without offline extraction or chromatographic separation. A RAMIP for amitriptyline was synthesised by the bulk method, using methacrylic acid as a functional monomer and glycidilmethacrylate as a hydrophilic co-monomer. Then, epoxide ring openings were made and the polymer was covered with bovine serum albumin (BSA). A column filled with RAMIP-BSA was coupled to a MS/MS instrument in an online configuration, using water as loading and reconditioning mobile phase and a 0.01% acetic acid aqueous solution: acetonitrile at 30:70 as elution mobile phase. The system was used for on-line extraction and simultaneous quantification of nortriptyline, desipramine, amitriptyline, imipramine, clomipramine and clomipramine-d3 (IS) (from 15.0 to 500.0μgL) from plasma samples. The correlation coefficient was higher than 0.99 for all analytes. The CV (coefficient of variation) values ranged from 1.34% to 19.13% for intra assay precision and 1.32-19.77% for inter assay precision. The E% (relative error) values ranged from -19.15% to 19.51% for intra assay accuracy and from -9.04% to 16.22% for inter assay accuracy.