LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients

J Chromatogr B Analyt Technol Biomed Life Sci. 2016 Aug 15:1028:111-119. doi: 10.1016/j.jchromb.2016.06.009. Epub 2016 Jun 7.

Abstract

Multiple myeloma (MM), a malignant neoplastic serum-cell disorder, has been a serious threat to human health. The determination of 6 commonly used drug concentrations, including thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin, in MM patients was of great clinical interest. Herein, we reported a method for the rapid and simultaneous measurement of the above therapeutics by liquid chromatography-tandem mass spectroscopy (LC-MS/MS) method with solid phase extraction. Analysis was performed on a Waters XBridge(®) BEH C18 column (2.5μm, 2.1 mm×50mm), with formic acid aqueous solution and acetonitrile as the mobile phase at flow rate 0.3mL/min. All analytes showed good correlation coefficients (r>0.996), and LLOQ of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin were 4, 2, 2, 2, 2 and 2ng/mL, respectively. The inter- and intra-day precisions and stability were expressed as variation coefficients within 15% and relative error less than 15%. Dilution effect, carryover and incurred sample reanalysis were investigated according to the 2015 edition Chinese Pharmacopoeia guidelines, as US FDA (2013, revision 1) required. The LC-MS/MS based assay described in this article may improve future clinical studies evaluating common therapeutics for MM treatment.

Keywords: Anti-cancer drug; Human serum; Liquid chromatography-tandem mass spectroscopy; Multiple myeloma patients.

Publication types

  • Validation Study

MeSH terms

  • Angiogenesis Inhibitors / blood
  • Antineoplastic Agents / blood*
  • Bortezomib / blood*
  • Chromatography, Liquid / methods
  • Cyclophosphamide / blood*
  • Dexamethasone / blood*
  • Doxorubicin / blood*
  • Drug Monitoring / methods
  • Humans
  • Immunosuppressive Agents / blood
  • Lenalidomide
  • Limit of Detection
  • Multiple Myeloma / blood
  • Multiple Myeloma / drug therapy
  • Tandem Mass Spectrometry / methods
  • Thalidomide / analogs & derivatives*
  • Thalidomide / blood*

Substances

  • Angiogenesis Inhibitors
  • Antineoplastic Agents
  • Immunosuppressive Agents
  • Thalidomide
  • Bortezomib
  • Dexamethasone
  • Doxorubicin
  • Cyclophosphamide
  • Lenalidomide