Covalent organic framework-based solid phase microextraction coupled with electrospray ionization mass spectrometry for sensitive screening and quantitative evaluation of carbamazepine and its metabolite in mice

Carbamazepine (CBZ) and its metabolite carbamazepine-10,11-epoxide (CBZEP) play vital role in the treatment of epilepsy. It is of great importance to develop a method for rapid and sensitive monitoring of CBZ and CBZEP due to their narrow therapeutic index. Herein, an imine-linked-based covalent organic framework was synthesized by using 1,3,5-tris (4-aminophenyl) benzene (TPB) and 1,3,5-triformylbenzene (TFB) (denoted as TPB-TFBCOF),and applied as a solid-phase microextraction (SPME) probe for extracting CBZ and CBZEP. The TPB-TFBCOF showed large surface areas (371 m(2) g(-1)), high regular porosity (1.23 nm) and extraordinary stability, which rendered it an ideal adsorbent for highly efficient enrichment of CBZ and CBZEP. Accordingly, an attractive strategy of the combination of the TPB-TFB-COF-based SPME probe and electrospray ionization mass spectrometry system (ESI/MS) was proposed for rapid screening and sensitive monitoring of CBZ and CBZEP. Under the optimized parameters, the developed method exhibited good linearity for CBZ and CBZEP in the range of 4-1000 mu g Lg(-1) with correlation coefficient (r) no less than 0.9953, and the corresponding limits of detection (LODs) were 0.4 and 2.5 mu g Lg(-1), respectively. Moreover, high enrichment factors (EFs, 202-351 folds) and satisfactory relative standard deviations (RSDs) of one probe (3.3-5.1%) and probe-to-probe (4.8-5.6%) were obtained. By using the proposed method, sensitive screening and quantitative evaluation of CBZ and CBZEP in mice whole blood and tissue homogenates were successfully achieved, indicating the promising applicability of the TPB-TFB-COF-SPME-AMIS as a powerful tool for drug monitoring.

Automated summary

In this study, an imine-linked-based covalent organic framework (TPB-TFBCOF) was synthesized and used as a solid-phase microextraction (SPME) probe for the efficient enrichment and monitoring of carbamazepine (CBZ) and carbamazepine-10,11-epoxide (CBZEP). The combination of the TPB-TFB-COF-based SPME probe and electrospray ionization mass spectrometry system (ESI/MS) enables rapid screening and sensitive monitoring of the target analytes. The method exhibits good linearity, low detection limits, high enrichment factors, and reliable repeatability.