A novel liquid-liquid-solid microextraction strategy for bio-sample preparation by in situ self-assembly of zeolitic imidazolate framework 8 on hollow fiber membrane

A novel liquid-liquid-solid membrane microextraction (LLSMME) method which integrates hollow fiber liquid phase microextraction (HF-LPME) and solid phase microextraction (SPME) was developed for bio-sample preparation. The homogeneous zeolitic imidazolate framework 8 mixed matrix membrane (ZIF-8-MMM) was prepared by in situ self-assembly of ZIF-8 on the inner surface of hollow fiber membrane and employed as a flexible LLSMME device. Incorporating the advantages of both HF-LPME and SPME, the as-fabricated ZIF-8-MMM exhibited excellent performance on the extraction and preconcentration of small molecule drugs of different polarity from complex biological matrices. As a case study, ZIF-8-MMM-based LLSMME coupled with UPLC-MS/MS were developed and validated for determination of ibuprofen, simvastatin and ranitidine at trace levels in rat plasma. The method showed good linearity (r² > 0.99) and repeatability (RSD < 15%), low limits of detection (2–3 ng mL⁻¹) and high relative recoveries (97.42–103.8%). The enrichment factors were between 87.3 and 112.6. Our study provided a promising strategy for developing more efficient, cost-effective and environmentally friendly technique for bio-sample pretreatment.