Citation: Chang Shu, Teng-Fei Li, Duo Li, Zhong-Qiu Li, Xing-Hua Xia. A sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide in human plasma and pharmacokinetic studies[J]. Chinese Chemical Letters, ;2022, 33(2): 916-919. doi: 10.1016/j.cclet.2021.07.009 shu

A sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide in human plasma and pharmacokinetic studies

Chang Shu ^{a, b} ,
Teng-Fei Li ^c ,
Duo Li ^b ,
Zhong-Qiu Li ^a ,
Xing-Hua Xia ^{a, *,}

a.
State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210023, China
b.
Department of Pharmaceutical Analysis, School of Pharmacy, China Pharmaceutical University, Nanjing 210009, China
c.
School of Pharmacy, Department of Clinical Pharmacology, Sir Run Hospital, Nanjing Medical University, Nanjing 211166, China

xhxia@nju.edu.cn

Received Date: 15 March 2021
Revised Date: 1 July 2021
Accepted Date: 2 July 2021
Available Online: 8 July 2021

Figures(2)

Pomalidomide is an immunomodulatory agent (IMiD) that has been approved by the US Food and Drug Administration (FDA) for clinical treatment of patients with multiple myeloma. In this work, we developed a sensitive and validated LC-MS/MS method for high-throughput determination of pomalidomide over the range of 1.006–100.6 ng/mL (R² = 0.9991) in human plasma and pharmacokinetic studies. A liquid-liquid extraction method using ethyl acetate was applied to extract pomalidomide and afatinib (as an internal standard, IS) from human plasma. Chromatographic separation was performed on a Hedera ODS column (150 mm × 2.1 mm, 5 µm) with security guard C18 column (4 mm × 2.0 mm) at 40 ℃. Methanol and 10 mmol/L aqueous solution of ammonium acetate containing 0.1% formic acid were used as a gradient elution mobile phase, and the flow rate was 0.4 mL/min. A triple quadruple tandem mass spectrometer using multiplex reaction monitoring mode (MRM) with electrospray ionization (ESI) positive ionization was employed. The precursor to product ion transitions for the quantitative analysis of pomalidomide and the IS were m/z 274.2→163.1 and m/z 486.1 → 371.1, respectively. This established method has been validated according to regulatory guideline, and the results were all within the acceptance criteria. The validated LC-MS/MS method was successfully applied to analyze samples obtained from clinical pharmacokinetics study after oral administration of pomalidomide (4 mg) capsules in human.
- Pomalidomide,
- Liquid-liquid extraction,
- LC–MS/MS method,
- Pharmacokinetic,
- Human plasma
1. [1]
  H. Chen, F. Chen, S. Pei, et al., Bioorg. Chem.87 (2019) 191–199. doi: 10.1016/j.bioorg.2019.03.035
2. [2]
  M.A. Dimopoulos, D. Dytfeld, S. Grosicki, et al., New Engl. J. Med. 379 (2018) 1811–1822. doi: 10.1056/nejmoa1805762
3. [3]
  C. Durer, S. Durer, S. Lee, et al., Blood Rev. 39 (2020) 100616. doi: 10.1016/j.blre.2019.100616
4. [4]
  E. Eleutherakis-Papaiakovou, M. Gavriatopoulou, I. Ntanasis-Stathopoulos, et al., Expert Rev. Anticancer Ther. 19 (2019) 921–928. doi: 10.1080/14737140.2019.1685879
5. [5]
  O. Fuchs, Cardiovasc Hematol Disord. Drug Targets19 (2019) 51–78. doi: 10.2174/1871529x18666180522073855
6. [6]
  R. Gopalakrishnan, H. Matta, B. Tolani, et al., Oncogene35 (2016) 1797–1810. doi: 10.1038/onc.2015.245
7. [7]
  M. Hagihara, S. Ide, S. Ohara, et al., Int. J. Clin. Oncol. 61 (2020) 20–26.
8. [8]
  K.M. Kortum, Y.X. Zhu, C.X. Shi, et al., Blood Rev. 29 (2015) 329–334. doi: 10.1016/j.blre.2015.03.003
9. [9]
  M.E. Matyskiela, W. Zhang, H.W. Man, et al., J. Med. Chem. 61 (2018) 535–542. doi: 10.1021/acs.jmedchem.6b01921
10. [10]
  S. Oka, K. Ono, M. Nohgawa, J. Clin. Pharm. Ther. 45 (2020) 221–225. doi: 10.1111/jcpt.13054
11. [11]
  C. Steinebach, S. Lindner, N.D. Udeshi, et al., ACS Chem. Biol. 13 (2018) 2771–2782. doi: 10.1021/acschembio.8b00693
12. [12]
  S. Su, Z. Yang, H. Gao, et al., J. Med. Chem. 62 (2019) 7575–7582. doi: 10.1021/acs.jmedchem.9b00871
13. [13]
  L. Sundaresan, P. Kumar, J. Manivannan, et al., Chem. Res. Toxicol. 32 (2019) 589–602. doi: 10.1021/acs.chemrestox.8b00286
14. [14]
  H.W. Tun, P.B. Johnston, L.M. DeAngelis, et al., Blood132 (2018) 2240–2248. doi: 10.1182/blood-2018-02-835496
15. [15]
  Z. Wang, N. He, Z. Guo, et al., J. Med. Chem. 62 (2019) 8152–8163. doi: 10.1021/acs.jmedchem.9b00919
16. [16]
  M. Dimopoulos, K. Weisel, N. van de Donk, et al., J. Clin. Oncol. 36 (2018) 2035–2043. doi: 10.1200/jco.2017.76.1742
17. [17]
  M. Iqbal, E. Ezzeldin, K.A. Al-Rashood, et al., J. Chromatogr. B983-984 (2015) 76–82. doi: 10.1016/j.jchromb.2014.12.036
18. [18]
  Y. Jiang, J. Wang, D.M. Rozewski, et al., J. Pharm. Biomed. Anal. 88 (2014) 262–268. doi: 10.1016/j.jpba.2013.08.036
19. [19]
  P. Lu, L. Wang, M. Song, et al., J. Pharm. Biomed. Anal. 114 (2015) 159–167. doi: 10.1016/j.jpba.2015.05.018
20. [20]
  Z.I. Szabo, L. Szocs, P. Horvath, et al., J. Sep. Sci. 39 (2016) 2941–2949. doi: 10.1002/jssc.201600354
21. [21]
  Y. Li, L. Liu, X. Wang, et al., J. Clin. Pharmacol. 58 (2018) 1295–1304. doi: 10.1002/jcph.1145
22. [22]
  Y. Li, X. Wang, L. Liu, J et al., Chin. Med. 10 (2018) 53–62. doi: 10.2147/CPAA.S167017
23. [23]
  Y. Li, X. Wang, L. Liu, et al., Clin. Pharmacol. Drug Dev. 8 (2019) 346–354. doi: 10.1002/cpdd.470
24. [24]
  Y. Li, Y. Xu, L. Liu, et al., J. Clin. Pharmacol. 55 (2015) 563–572. doi: 10.1002/jcph.455
25. [25]
  K. Matsue, H. Iwasaki, T. Chou, K. et al., Cancer Sci. 106 (2015) 1561–1567. doi: 10.1111/cas.12772
26. [26]
  M.N. Polizzotto, T.S. Uldrick, K.M. Wyvill, et al., J. Clin. Oncol. 34 (2016) 4125–4131. doi: 10.1200/JCO.2016.69.3812
1. [1]
  Guo-Ping Yin , Ya-Juan Li , Li Zhang , Ling-Gao Zeng , Xue-Mei Liu , Chang-Hua Hu . Citrinsorbicillin A, a novel homotrimeric sorbicillinoid isolated by LC-MS-guided with cytotoxic activity from the fungus Trichoderma citrinoviride HT-9. Chinese Chemical Letters, 2024, 35(8): 109035-. doi: 10.1016/j.cclet.2023.109035
2. [2]
  Cheng Guo , Xiaoxiao Zhang , Xiujuan Hong , Yiqiu Hu , Lingna Mao , Kezhi Jiang . Graphene as adsorbent for highly efficient extraction of modified nucleosides in urine prior to liquid chromatography-tandem mass spectrometry analysis. Chinese Chemical Letters, 2024, 35(4): 108867-. doi: 10.1016/j.cclet.2023.108867
3. [3]
  Haoyang Wang , Ronghao Zhang , Yanlun Ren , Li Zhang . A convenient method for measuring gas-liquid volumetric mass transfer coefficient in micro reactors. Chinese Chemical Letters, 2024, 35(4): 108833-. doi: 10.1016/j.cclet.2023.108833
4. [4]
  Yihong Li , Zhong Qiu , Lei Huang , Shenghui Shen , Ping Liu , Haomiao Zhang , Feng Cao , Xinping He , Jun Zhang , Yang Xia , Xinqi Liang , Chen Wang , Wangjun Wan , Yongqi Zhang , Minghua Chen , Wenkui Zhang , Hui Huang , Yongping Gan , Xinhui Xia . Plasma enhanced reduction method for synthesis of reduced graphene oxide fiber/Si anode with improved performance. Chinese Chemical Letters, 2024, 35(11): 109510-. doi: 10.1016/j.cclet.2024.109510
5. [5]
  Tong Zhang , Xiaojing Liang , Licheng Wang , Shuai Wang , Xiaoxiao Liu , Yong Guo . An ionic liquid assisted hydrogel functionalized silica stationary phase for mixed-mode liquid chromatography. Chinese Chemical Letters, 2025, 36(1): 109889-. doi: 10.1016/j.cclet.2024.109889
6. [6]
  Hongxia Li , Xiyang Wang , Du Qiao , Jiahao Li , Weiping Zhu , Honglin Li . Mechanism of nanoparticle aggregation in gas-liquid microfluidic mixing. Chinese Chemical Letters, 2024, 35(4): 108747-. doi: 10.1016/j.cclet.2023.108747
7. [7]
  Pengyu Chen , Beibei Chen , Man He , Yuxi Zhou , Lei Lei , Jian Han , Bingsheng Zhou , Ligang Hu , Bin Hu . Nanoplastics and nano-ZnO facilitate Cd accumulation in zebrafish larvae via a distinct pathway: Revelation by LA-ICP-MS imaging. Chinese Chemical Letters, 2025, 36(2): 109908-. doi: 10.1016/j.cclet.2024.109908
8. [8]
  Quan Zhang , Shunjie Xing , Jingqian Han , Li Feng , Jianchun Li , Zhaosheng Qian , Jin Zhou . Organic pollutant sensing for human health based on carbon dots. Chinese Chemical Letters, 2025, 36(1): 110117-. doi: 10.1016/j.cclet.2024.110117
9. [9]
  Tian Feng , Yun-Ling Gao , Di Hu , Ke-Yu Yuan , Shu-Yi Gu , Yao-Hua Gu , Si-Yu Yu , Jun Xiong , Yu-Qi Feng , Jie Wang , Bi-Feng Yuan . Chronic sleep deprivation induces alterations in DNA and RNA modifications by liquid chromatography-mass spectrometry analysis. Chinese Chemical Letters, 2024, 35(8): 109259-. doi: 10.1016/j.cclet.2023.109259
10. [10]
  Wangyan Hu , Ke Li , Xiangnan Dou , Ning Li , Xiayan Wang . Nano-sized stationary phase packings retained by single-particle frit for microchip liquid chromatography. Chinese Chemical Letters, 2024, 35(4): 108806-. doi: 10.1016/j.cclet.2023.108806
11. [11]
  Yang Li , Yihan Chen , Jiaxin Luo , Qihuan Li , Yiwu Quan , Yixiang Cheng . Enhanced circularly polarized luminescence emission promoted by achiral dichroic oligomers of F8BT in cholesteric liquid crystal. Chinese Chemical Letters, 2024, 35(11): 109864-. doi: 10.1016/j.cclet.2024.109864
12. [12]
  Yuqing Ding , Zhiying Yi , Zhihui Wang , Hongyu Chen , Yan Zhao . Liquid nitrogen post-treatment for improved aggregation and electrical properties in organic semiconductors. Chinese Chemical Letters, 2024, 35(12): 109918-. doi: 10.1016/j.cclet.2024.109918
13. [13]
  Jianwen Zhao , Shuai Wang , Shanshan Zhao , Liwei Chen , Fangang Meng , Xuelin Tian . A non-fluorinated liquid-like membrane with excellent anti-scaling performance for membrane distillation. Chinese Chemical Letters, 2025, 36(1): 109883-. doi: 10.1016/j.cclet.2024.109883
14. [14]
  Jiajia Wang , XinXin Ge , Yajing Xiang , Xiaoliang Qi , Ying Li , Hangbin Xu , Erya Cai , Chaofan Zhang , Yulong Lan , Xiaojing Chen , Yizuo Shi , Zhangping Li , Jianliang Shen . An ionic liquid functionalized sericin hydrogel for drug-resistant bacteria-infected diabetic wound healing. Chinese Chemical Letters, 2025, 36(2): 109819-. doi: 10.1016/j.cclet.2024.109819
15. [15]
  Wantong Zhang , Zixing Xu , Guofei Dai , Zhijian Li , Chunhui Deng . Removal of Microcystin-LR in lake water sample by hydrophilic mesoporous silica composites under high-throughput MALDI-TOF MS detection platform. Chinese Chemical Letters, 2024, 35(5): 109135-. doi: 10.1016/j.cclet.2023.109135
16. [16]
  Wenbi Wu , Yinchu Dong , Haofan Liu , Xuebing Jiang , Li Li , Yi Zhang , Maling Gou . Modification of plasma protein for bioprinting via photopolymerization. Chinese Chemical Letters, 2024, 35(8): 109260-. doi: 10.1016/j.cclet.2023.109260
17. [17]
  Jun-Jie Fang , Zheng Liu , Yun-Peng Xie , Xing Lu . Superatomic Ag₅₈ nanoclusters incorporating a [MS₄@Ag₁₂]²⁺ (M = Mo or W) kernel show aggregation-induced emission. Chinese Chemical Letters, 2024, 35(10): 109345-. doi: 10.1016/j.cclet.2023.109345
18. [18]
  Yanhua Chen , Xian Ding , Jun Zhou , Zhaoying Wang , Yunhai Bo , Ying Hu , Qingce Zang , Jing Xu , Ruiping Zhang , Jiuming He , Fen Yang , Zeper Abliz . Plasma metabolomics combined with mass spectrometry imaging reveals crosstalk between tumor and plasma in gastric cancer genesis and metastasis. Chinese Chemical Letters, 2025, 36(1): 110351-. doi: 10.1016/j.cclet.2024.110351
19. [19]
  Luyu Zhang , Zirong Dong , Shuai Yu , Guangyue Li , Weiwen Kong , Wenjuan Liu , Haisheng He , Yi Lu , Wei Wu , Jianping Qi . Ionic liquid-based in situ dynamically self-assembled cationic lipid nanocomplexes (CLNs) for enhanced intranasal siRNA delivery. Chinese Chemical Letters, 2024, 35(7): 109101-. doi: 10.1016/j.cclet.2023.109101
20. [20]
  Feng-Qing Huang , Yu Wang , Ji-Wen Wang , Dai Yang , Shi-Lei Wang , Yuan-Ming Fan , Raphael N. Alolga , Lian-Wen Qi . Chemical isotope labeling-assisted liquid chromatography-mass spectrometry enables sensitive and accurate determination of dipeptides and tripeptides in complex biological samples. Chinese Chemical Letters, 2024, 35(11): 109670-. doi: 10.1016/j.cclet.2024.109670

Get Citation

PDF

XML

Metrics

PDF Downloads(11)
Abstract views(810)
HTML views(100)

通讯作者: 陈斌, bchen63@163.com

1.
沈阳化工大学材料科学与工程学院沈阳 110142