The objective of this analysis is to establish the potential of biodegradable agro-industrial waste materials as biosorbents in the solid-phase extraction (SPE) technique for sample preparation. In this regard, waste coffee husk (CH) powder was collected, washed, treated chemically, characterized, and applied as an SPE adsorbent to extract pantoprazole from the wastewater samples. Sample detection was accomplished using the UPLC-MS/MS system. The positive mode of electrospray ionization was exploited for the ionization of the sample, and quantification of the target analyte was performed by the multiple reaction monitoring modes. The precursor to product ion transition of 384.02→1380.05 and 384.02→200.05 was used as qualifiers and quantifiers, respectively. Optimization of the particle size, adsorbent dose, and contact time were evaluated to select the best combination of features. The efficiency and regeneration capability of the CH were compared with respect to a commercially available silica-based C18 SPE adsorbent, and it was found that CH possessed comparable (~50%) extraction, as well as regeneration capacity (~95%). The developed biosorbent was applied in a wastewater sample spiked with the target analyte and recovery studies were performed, which found a range of 93.0 to 102.0% with a %RSD of 3.72 to 12.7%. Thus, CH can be exploited as a ‘greener’ replacement for the commercially available adsorbents for the extraction/retention of active pharmaceutical ingredients present in water/wastewater samples.