Performant sample preparation is mandatory in any leachable study to clean and preconcentrate analytes within the sample to offer the best possible extraction recovery as well the best precision for any given substance. The aim consists in developing a sample preparation method for hospital pharmacy-prepared drug products such as long-term storage prefilled syringes, vials and IV bags for the screening of leachable compounds. The Quality Control Laboratory of the Pharmacy of the Lausanne University Hospital (Switzerland) has developed a time- and cost-effective, highly sensitive, robust, and fast method using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for the analysis of 205 plastic additives. An innovative setup, based on postcolumn infusion (PCI) using 2% ammonium hydroxide in methanol was used to boost the signal intensity of the analytes in MS detection. A database for extractable and leachable trace assessment (DELTA) was built to assist in the screening process of 205 plastic packaging-related compounds. The development of the sample preparation was based on 33 plastic additive candidates in different hospital pharmacy compounding solutions, and their extraction recovery rates as well as their relative standard deviation were taken into consideration. In conclusion, the developed DLLME was assigned with ultrasound assistance and triple extraction, which brought about extraction recovery rates between 67% and 92%, a good RSD <10%, and a preconcentration factor of 50×. Therefore, DLLME could be considered suitable for the semiquantitative screening of leachable additives in simple hospital pharmacy-prepared prefilled drug products.