2. Academic Validation
  3. Detection of lenalidomide metabolites in urine to discover drug-resistant compounds

Detection of lenalidomide metabolites in urine to discover drug-resistant compounds

  • Clin Chim Acta. 2023 Dec 14:117707. doi: 10.1016/j.cca.2023.117707.
Xiaokai Zhan 1,  Xikun Liu 2,  Li Rang 3,  Man Shen 4,  Jiajia Zhang 4,  Ran Tang 4,  Sibin Fan 4,  Fengyi Zhao 4,  Xin Li 4,  Xiaoying Zhang 5,  Zhongxia Huang 6,  Sen Zhang 5
Affiliations

Affiliations

  • 1 Division of Oncology and hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, PR China. Electronic address: [email protected].
  • 2 State key laboratory of bioactive substances and functions of natural medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, 1 Xian Nong Tan Street, Xicheng District, Beijing, 100050, PR China.
  • 3 Pathology Department, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, PR China.
  • 4 Division of Oncology and hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, PR China.
  • 5 State key laboratory of bioactive substances and functions of natural medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union medical college, 1 Xian Nong Tan Street, Xicheng District, Beijing, 100050, PR China. Electronic address: [email protected].
  • 6 Division of Oncology and hematology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, PR China. Electronic address: [email protected].
PMID: 38103853 DOI: 10.1016/j.cca.2023.117707
Abstract

Lenalidomide is the first-line drug for the clinical treatment of multiple myeloma. However, its efficacy differs significantly among patients. Clinically, after lenalidomide treatment, few patients' conditions worsened, whereas Others remained stable or improved. To clarify the reasons for this difference in efficacy, 20 patients with multiple myeloma who received maintenance treatment with lenalidomide were retrospectively included in this study. Lenalidomide metabolic compounds were detected in patient urine using mass spectrometry. A rapid and accurate ultra-performance liquid chromatography-time-of-flight tandem mass spectrometry (UPLC-TOF-MS/MS) method was used to characterize metabolites in the urine of different patients. Eleven metabolites, including four new compounds, were identified and characterized in all the samples. Among these, two metabolites were found to have obvious discrepancies in different groups of patients. One metabolite named Denitrified-2 glutarimide, a new potential compound, was only detected in the urine of ineffective and stable patients, whereas the other metabolite named 5-Hydroxy-lenalidomide was found only in the urine of effective patients.

Keywords

Drug resistance; Lenalidomide; UPLC-TOF-MS/MS; Urine metabolism.

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