Tailoring a MOF-on-MOF (ZIF-8-on-NH2-MIL-53(Al)) Hybrid Composite for Micro Solid Phase Extraction of Furosemide in artificial biological fluids prior to LC-q-TOF/MS detection

• A 'ZIF-8-on-NH2-MIL-53(Al)' was used as a composite. • VA-µ-SPE provided faster and higher extraction efficiency. • The sensitivity of the VA-µ-SPE-LC-q-TOF/MS process was increased. • Furosemide in biological matrices was determined by a sensitive method. Furosemide, a powerful diuretic that increases urine excretion, is used to treat many diseases. However, due to its abuse in sport, it is considered a doping substance. As a result, it has been banned by the World Anti-Doping Agency (WADA) and included in the group of diuretics and masking agents. Given the clinical significance of furosemide and its dependable application in athletics, this research employed the "MOF-on-MOF" hybrid material composite to leverage the synergistic effects of various components for detecting this drug in biological samples. After characterization of the ZIF-8-on-NH 2 -MIL-53(Al) composite by FT-IR, XRD, TGA, XPS, BET and SEM-EDX techniques, the µ-SPE procedure was optimized using liquid chromatography-time of flight mass spectrometry (LC-q-TOF/MS) based on the recovery values. The optimum conditions were determined as pH 6, adsorbent amount of 20 mg, and total adsorption-desorption time of 7 min. The recovery values of the solid-phase extraction method for simulated body fluids samples under optimum conditions were between 77.5 % and 93.4 %. The µ-SPE technique was effectively utilized on physiological samples using the ZIF-8-on-NH 2 -MIL-53(Al) composite under optimal conditions. This study's findings will inform future research into the design of 'MOF-on-MOF' hybrids for various applications.