The growing and decelerated presence of pharmaceutically active compounds that affect networks of tap water is further studied due to the risks to the health public and the environment. Therefore, a direct injection-HPLC/MS-MS method is developed for the simultaneous determination of 16 active pharmaceutical compounds in tap water samples: amoxicillin, ampicillin, cephalexin, cefotaxime, cefuroxime, cipro oxacin, clarithromycin, clindamycin, chloramphenicol, cyproterone, erythromycin, utamide, spironolactone, sulfamethoxazole, tamoxifen, and trimethoprim. The implemented method obtained limits of detection (LOD) of 0.3 -15 µg/L and quanti cation limits (LOQ) from 1.5 to 50 µg/L, recoveries percentages in the range of 70 -125%, time retentions ≤ 2.1 min and allowed the analysis of 22 tap water samples where the highest concentrations corresponding to amoxicillin (147 µg/L) and cipro oxacin (44 µg/L). The ndings in this research could be a precedent for establishing safe levels of these compounds and increasing the standards for quality tap water.