Prefilled plastic packaging is time- and cost-effective in hospital pharmacy because it prevents waste, preparation errors, dosage errors, microbial contamination and accidents. This packaging mostly includes prefilled syringes (PFS), intravenous (IV) bags and vials intended for long-term storage that can be used for immediate treatment. There is a rising availability in the market for prefilled drug products due to their practical approach. Leachable compounds could be evaluated in hospital pharmacy-prepared prefilled drug solutions. The Pharmacy Department at the Lausanne University Hospital has developed an innovative, highly sensitive, and generic method by postcolumn infusion based on ultrahigh-performance liquid chromatography coupled to high-resolution mass spectrometry (LC-HRMS) for the analysis of plastic additives in hospital pharmacies. The postcolumn infusion solution was developed with 2% ammonium hydroxide in methanol on a representative set of 30 candidate compounds with different physical-chemical properties, such as log P and molecular structure, to represent the most important categories of additives. The LODs obtained for all compounds ranged from 0.03 to 7.91 ng/mL with linearity up to 250 ng/mL. Through this screening method, plastic additives can be rapidly identified due to the combined use of retention time, exact mass (including isotopic pattern) and MS/MS spectra. In addition, the users can screen for vast categories of plastic additives, including plasticizers, epoxy monomers, antioxidants, UV stabilizers, and others. The screening is facilitated by assessments of a complex in-house-built database for extractable and leachable trace assessment (DELTA), containing 205 compounds for unambiguous identification. Relative response factors were established for all analytes to obtain a semiquantitation of compounds. Moreover, the database also contains valuable estimative toxicology information, which was obtained through calculating their permissible dose exposure threshold; thus, estimative toxicology assessment can be performed for identified compounds in prefilled drug products. This method and the database were applied to a hospital pharmacy-prepared prefilled vancomycin syringe for paediatric use. Ultrasound-assisted dispersive liquid-liquid microextraction (UA-DLLME) was used to prepare the samples for leachable analysis. As a result, 17 plastic additives were formally identified, and their concentrations were estimated. A toxicology assessment was performed by comparing their concentrations with their theoretical PDE thresholds. In conclusion, the prefilled drug solution released a negligible amount of known leachables that appeared to be safe for use in neonates and children.