Total reflection X-ray fluorescence (TXRF) is becoming more and more popular for elemental analysis in academia and industry. However, simplification of the procedures for analyzing samples with complex compositions and residual matrix effects is still needed. In this work, the effect of an inorganic (CaCl2) and an organic (tetraalkylphosphonium chloride) matrix on metals quantification by TXRF was investigated for liquid samples. The samples were spiked with up to 20 metals at concentrations ranging from 3 to 50 mg L-1 per element, including elements with spectral peaks near the peaks of the matrix elements or near the Raleigh and Compton scattering peaks of the X-ray source (molybdenum anode). The recovery rate (RR) and the relative standard deviation (RSD) were calculated to express the accuracy and the precision of the measured element concentrations. In samples with no matrix effects, good RRs are obtained regardless of the internal standard selected. However, in samples with moderate matrix content, the use of an optimum internal standard (OIS) at a concentration close to that of the analyte significantly improved the quantitative analysis. In samples with high concentrations of inorganic ions, using a Triton X-100 aqueous solution to dilute the sample during the internal standardization resulted in better RRs and lower RSDs compared to using only water. In samples with a high concentration of organic material, pure ethanol gave slightly better results than when a Triton X-100-ethanol solution was used for dilution. Compared to previous methods reported in the literature, the new sample-preparation method gave better accuracy, precision, and sensitivity for the elements tested. Sample dilution with an OIS and the surfactant Triton X-100 (inorganic media) or ethanol (organic media) is recommended for fast routine elemental determination in matrix containing samples, as it does not require special equipment, experimentally derived case-dependent mathematical corrections, or physicochemical removal of interfering elements.