Determination of five mTOR inhibitors in human plasma for hepatocellular carcinoma treatment using QuEChERS-UHPLC-MS/MS

  • J Pharm Biomed Anal. 2023 Oct 25:235:115652. doi: 10.1016/j.jpba.2023.115652.
Ting Wang  1 ,  Chengcheng Jin  1 ,  Wen Jiang  1 ,  Tingting Zhao  2 ,  Yanmei Xu  3 ,  Hui Li  4
Affiliations
  • 1. College of Chemistry and Pharmaceutical Engineering, Hebei University of Science and Technology, Shijiazhuang, China.
  • 2. College of Pharmacy, Hebei Medical University, Shijiazhuang 050000, China.
  • 3. Hebei Institute of Drug and Medical Device Inspection, Shijiazhuang, China.
  • 4. Hebei Institute of Drug and Medical Device Inspection, Shijiazhuang, China. Electronic address: [email protected].
PMID: 37633163 DOI: 10.1016/j.jpba.2023.115652
Abstract

A fast and reliable QuEChERS (Quick, Easy, Cheap, Effective, Rugged, and Safe) method for pre-processing combined with Ultra - high performance liquid chromatography - tandem mass spectrometry (UHPLC-MS/MS) was established for the analysis of five mammalian rapamycin target protein (mTOR) inhibitors (vistusertib, AZD8055, pictilisib, everolimus, temsirolimus)in human plasma. Extraction was achieved by addition of acetonitrile to the sample followed by anhydrous magnesium sulfate and 30 mg C18 for salting out and purification, respectively. mTOR inhibitors were detected using selective response monitoring (SRM) under positive ion electrospray mode. Vistusertib, AZD8055 and pictilisib showed good linearity with a range of 1-80 ng/ml, Additionally, the concentration of everolimus and temsirolimus was 2.5-200 ng/ml and10-800 ng/ml, respectively. The linear correlation coefficient (R2) of each analysis was ≥ 0.9950. The limit of detection (LOD) and Limit of Quantitation (LOQ) were 0.015-0.75 ng/ml and 1-10 ng/ml, respectively. This method showed a high accuracy with high recovery rate and excellent stability. This method is fast, accurate and reliable, suitable for quantitative detection of mTOR inhibitors in human plasma.

Keywords
Human plasma; Mammalian target of rapamycin inhibitors; QuEChERS; UHPLC-MS/MS.
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