Rapid simultaneous determination of ketamine and midazolam in biological samples using ion mobility spectrometry combined by headspace solid-phase microextraction.

Ketamine (Ket) and midazolam (Mdz) are among well-known anesthetic agents which frequently coadministered in surgical procedures and emergency department. Only a few reports have been published for the simultaneous analysis of these compounds. In the present study, we reported a simple, sensitive, and rapid method for simultaneous determination of Ket and Mdz based on headspace solid-phase microextraction coupled with ion mobility spectrometry (HS-SPME-IMS). Ion mobility spectrometer operated under positive mode of a corona discharge ionization source using ammonia as a dopant. The effective parameters on the extraction process consisting of pH of the sample, extraction temperature, extraction time, salt concentration were optimized. The calibration plots exhibited good linearity over the concentration ranges of 10-800 and 100-1500 µg L and detection limit of 8.9 and 52 µg L for Ket and Mdz respectively with correlation coefficients greater than 0.99. The relative standard deviation (RSD) for five replicate measurements was determined to be less than 8%. Finally, the applicability of the proposed method was tested in human plasma and serum samples. These tests showed that the matrix in serum samples interfere with midazolam determination but quantitative recoveries from 85 to 95 % were obtained for both drugs in the human plasma samples. The method herein provides simple and suitable approach while minimizing sample preparation and the overall complexity of the analysis in comparison to existing methodologies.