Rapid determination of memantine in human plasma by using nanoring carboxyl‐functionalized paramagnetic molecularly imprinted polymer d‐μ‐SPE and UFLC‐MS/MS

Abstract

A novel, simple, and sensitive method based on the use of dispersive micro-solid-phase extraction (d-μ-SPE) procedure combined with ultra-fast liquid chromatography-tandem quadrupole mass spectrometry (UFLC-MS/MS) for the determination of memantine (ME) was developed and validated over the linearity range 0.05-10.0 µg/L with 100 μL of human plasma using memantine-D6 (ME-D6) as the internal standard. The novel nanoring carboxyl-functionalized paramagnetic molecularly imprinted polymer (NR-CF-Mag-MIP) was synthesized by ultrasound-assisted suspension polymerization, using ME as a template molecule, methacrylic acid as a functional monomer, and divinylbenzene as a cross-linking agent. The NR-CF-Mag-MIP was used as the d-μ-SPE sorbent to extract ME from human plasma samples. The obtained results demonstrated the higher extraction capacity of NR-CF-Mag-MIP with recoveries between 97.6 and 101%. The limits of quantification (LOQs) for ME was 0.015 µg/L. Validation results on linearity, specificity, accuracy, precision, and stability, as well as on application to the analysis of samples taken up to 480 h after oral administration of 20 mg (two 10 mg capsules) of ME in healthy volunteers demonstrated the applicability to bioequivalence studies.

Pharmacokinetic Drug-Drug Interaction and Responsible Mechanism between Memantine and Cimetidine

“…The newly developed analytical method for memantine using an LC-MS/MS system showed comparable sensitivity (i.e., LLoQ 0.2 ng/mL) as previously published methods (i.e., LLoQ 0.1–1 ng/mL) despite the use of a small volume (50 μL) of plasma samples compared with previous methods [ 7 , 27 , 28 , 29 , 30 , 31 ]. Additionally, previously established methods used solid-phase extraction or liquid-liquid extraction which requires costly reagents and large volume of plasma samples (100–1000 μL) [ 27 , 28 , 29 , 30 , 31 ]. Noetzli et al applied the protein-precipitation method and sample preparations were processed by evaporation and reconstitution [ 29 ].…”