“…Although these procedures isolate and enhance the response of the target analyte, they are often time consuming, difficult to automate, reduce precision and incur sample loss. Several different pre-analytical protocols have been employed to minimize the deleterious effects of complex biofluid matrices, with liquid-liquid extraction (LLE) [15][16][17][18][19][20][21][22][23][24] and solid-phase extraction (SPE) [25][26][27][28][29][30] being the most common for these analytes. Once isolated from the matrix, numerous analytical techniques have been used for multiplex methylxanthine analyses including radioimmunoassay (RIA) [31], thin-layer chromatography (TLC) [26], capillary gas chromatography (GC) [32] and micellar electrokinetic electrophoresis (MEKC) [33,34].…”