Aerogel Pore‐Confined High‐Loading MOF‐199 for Micro‐Solid‐Phase Extraction of Methorphan Enantiomer in Biological Samples

ABSTRACT

Dextromethorphan is a widely used clinical antitussive, while its enantiomer, levomethorphan, is a controlled substance. Chiral separation and trace detection of the two enantiomers in biological samples are critically important. Herein, a micro‐solid‐phase extraction method coupled with enantioselective ultra‐high performance liquid chromatography–mass spectrometry (UHPLC–MS) was proposed for the analysis of methorphan enantiomers. MOF‐199/cellulose aerogel spheres fabricated via a facile in situ growth strategy were employed as the sorbent. By immersing Cu ²⁺ ‐rich cellulose aerogel in H ₃ BTC (1,3,5‐benzene tricarboxylate) solutions at varied concentrations, MOF‐199/cellulose aerogels with tunable MOF‐199 loadings (28.8%, 38.1%, 43.8%) were fabricated. Characterization results verified that MOF‐199 was uniformly anchored in the pore channels of cellulose aerogel, which not only enhanced its specific surface area from 33.9 to 143.6 m ² /g, but also mitigated the aggregation and poor recyclability of powdered MOF‐199. The electrostatic attraction, chelation, and hydrogen‐bonding interactions accounted for the effective extraction for dextro‐ and levo‐methorphan. Under optimized conditions, this method exhibited favorable linearity in the range of 0.02–10.0 µg/L, with intra‐ and inter‐day precisions of 4.9%–5.0% and 7.7%–9.7%, respectively. The limits of detection were 0.01–0.02 µg/L, respectively. Recoveries of dextro‐ and levo‐methorphan from urine and hair samples were in the ranges of 88.9%–119.3% and 78.6%–115.7%, respectively. This method provides an effective strategy for the determination of methorphan enantiomers in biological samples, featuring rapid pretreatment, low organic solvent consumption, as well as facile operation.