title: LC-MS/MS method for simultaneous determination of thalidomide, lenalidomide, cyclophosphamide, bortezomib, dexamethasone and adriamycin in serum of multiple myeloma patients.
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.
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Chang
authors.initials: C
authors.lastname: Shu
authors.affiliation: Department of Oncology, Eastern Hepatobiliary Hospital, Second Military Medical University, 700 North moyu Road, Shanghai 201805, PR China.
authors.forename: Tianmei
authors.initials: T
authors.lastname: Zeng
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Shouhong
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Tianyi
authors.initials: T
authors.lastname: Xia
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China.
authors.forename: Lifeng
authors.initials: L
authors.lastname: Huang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China. Electronic address: zhangfeng@smmu.edu.cn.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of Pharmacy, Changzheng Hospital, Second Military Medical University, 415 Fengyang Road, Shanghai 200003, PR China. Electronic address: chenwansheng@smmu.edu.cn.
authors.forename: Wansheng
authors.initials: W
authors.lastname: Chen
mesh_terms: D020533:Angiogenesis Inhibitors / Q000097:blood; D000970:Antineoplastic Agents / Q000097:blood*; D000069286:Bortezomib / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods; D003520:Cyclophosphamide / Q000097:blood*; D003907:Dexamethasone / Q000097:blood*; D004317:Doxorubicin / Q000097:blood*; D016903:Drug Monitoring / Q000379:methods; D006801:Humans; D007166:Immunosuppressive Agents / Q000097:blood; D000077269:Lenalidomide; D057230:Limit of Detection; D009101:Multiple Myeloma / Q000097:blood / Q000188:drug therapy; D053719:Tandem Mass Spectrometry / Q000379:methods; D013792:Thalidomide / Q000031:analogs & derivatives* / Q000097:blood*
chemical_list: D020533:Angiogenesis Inhibitors; D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone; D004317:Doxorubicin; D003520:Cyclophosphamide; D000077269:Lenalidomide
keywords: Anti-cancer drug; Human serum; Liquid chromatography-tandem mass spectroscopy; Multiple myeloma patients