The high sensitivity of our method with LOD values mostly <0.05 ng mL -1 generally outperformed previously published, more tailored multi-class assays, that feature a far smaller number of xenobiotics (see Supplementary Table ). This was possible by the application of an effective chromatographic separation, NH4F as ionization additive, and the latest generation LC-MS instrumentation. Our approach employs a simple and rapid, yet comprehensive, sample extraction procedure that enabled the concurrent detection of almost 30 highly-diverse exposures in blood and breast milk samples obtained from a reallife cohort. In particular, breast milk posed an analytical challenge due to the complexity of the matrix. Thereby, we demonstrated that if the newest generation of LC-MS/MS instrumentation is utilized in a more holistic manner, non-tailormade methods to analyze chronic exposure levels are feasible. One drawback of targeted analyses is, however, that conjugated chemicals are often not included in mass transition lists and are therefore overlooked. Hence, the developed LC-MS/MS method also includes some glucuronides and sulfates; albeit only a limited number of analytes are included as reference standards of phase II metabolites are rarely commercially available. As the volumes of the available materials were mostly sufficient for only one sample preparation, an enzymatic deconjugation of the neonate plasma samples was only tested for a few samples in this work. In addition, all breast milk samples were enzymatically treated and re-measured. However, after application of a crude enzyme extract (β-glucuronidase and sulfatase from Helix pomatia) increased baseline noise was observed. As the method was analytically validated without enzymatic treatment, this resulted in issues with selectivity and sensitivity (i.e. previous detections could not be replicated) for some compounds. Further, the enzyme solution was shown to be contaminated with many of the included analytes, resulting in the introduction of contamination. Nonetheless, the experiments confirmed the assumption that, for chemicals where the newly introduced enzyme-matrix did not result in severe analytical interference, increased toxicant concentrations can be obtained. In future studies, this approach has the potential to increase the number and concentrations of the xenobiotics detected, most notably in urine, following thorough re-validation. The use of proteolytic enzymes (e.g. pronase) in future work might be considered if highly electrophilic molecules with an affinity for albumin/protein adducts are in focus.