Determination of Vorinostat and M2 Metabolites in Human Serum by High Performance Liquid Chromatography-Mass Spectrometric_West China Medical Journal

Authors：

 MeiYajun ^1,2 ,  QinYongping ¹ , ZhangLi ¹ , NanFeng ¹ , XiangJin ¹ , YuQin ¹ , LiangMaozhi ¹

1. Laboratory of Clinical Pharmacology GCP Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China;
2. College of Pharmacy, Chengdu University of TCM, Chengdu, Sichuan 611137, P. R. China;

Corresponding author：

QinYongping, Email: qinypingl@163.com

Keywords：

High performance liquid chromatography-mass spectrometric; Vorinostat; M2 metabolite; Drug concentration in plasma

DOI：

10.7507/1002-0179.20160075

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Objective To establish an accurate and sensitive high performance liquid chromatography-mass spectrometric (HPLC/MS/MS) method for determination of vorinostat (SHA) and M2 metabolites in human serum, which was applicable for pharmacokinetic study of SHA. Methods The essay was conducted with an API 3000 HPLC-MS/MS system consisted of a Gemini C18 column (50 mm×3 mm, 3 μm), and the mobile phase consisted of methanol-acetonitrile-water-1 mol/L NH3-formic acid (25:15:60:0.1:0.05) at a flow rate of 0.23 mL/min. Acidulated serum samples were extracted by 3.5 mL diethyl ether which contains 3% isopropyl alcohol and was operated under the multiple reaction monitoring mode using the electrospray ionization technique. d5-SHA was used as the internal standard. Results The retention time of SHA, M2 metabolite and internal standard were 4.1, 3.1 and 4.0 minutes, respectively. The linear range of SHA and M2 metabolite were in the range of 1-1 000 and 2-2 000 ng/mL, and the limit of quantity were 1.0 and 2.0 ng/mL; the method recovery were 93.0%-99.3% and 88.11%-104.12%, respectively. Matrixes effect of SHA and M2 metabolite were blow 9.0%. Conclusion This method for the quantitative determination of SHA and M2 in human serum was proved to be simple, rapid, sensitive and accurate; it can be applied in the determination of SHA and M2 metabolite.

Citation： MeiYajun, QinYongping, ZhangLi, NanFeng, XiangJin, YuQin, LiangMaozhi. Determination of Vorinostat and M2 Metabolites in Human Serum by High Performance Liquid Chromatography-Mass Spectrometric. West China Medical Journal, 2016, 31(2): 278-282. doi: 10.7507/1002-0179.20160075 Copy

1.	Yoo CB, Jones PA. Epigenetic therapy of cancer:past, present and future[J]. Nat Rev Drug Discov, 2006, 5(1):37-50.
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11.	楼文珠, 孙雪燕, 李龙珠, 等. 组蛋白脱乙酰酶抑制剂的抗癌作用[J]. 中国细胞生物学学报, 2011(9):1045-1052.
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13.	Crump M, Coiffier B, Jacobsen ED, et al. Phase Ⅱ trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma[J]. Ann Oncol, 2008, 19(5):964-969.
14.	Vansteenkiste J, Van Cutsem E, Dumez H, et al. Early phase Ⅱ trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer[J]. Invest New Drugs, 2008, 26(5):483-488.
15.	Blumenschein GJ, Kies MS, Papadimitrakopoulou VA, et al. PhaseⅡtrial of the histone dea cetylase inhibit or vorinostat (Zolinz, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer[J]. Invest New Drugs, 2008, 26(1):81-87.
16.	杜晓琅, 朱贺, 丁黎, 等. 液相色谱-串联质谱法同时测定人血清与尿液中伏立诺他及其代谢物4-苯胺基-4-氧代丁酸的浓度[J]. 中国新药与临床杂志, 2012, 31(7):385-391.
17.	Du L, Musson DG, Wang AQ. High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum[J]. Rapid Commun Mass Spectrom, 2005, 19(13):1779-1787.
18.	Parise RA, Holleran JL, Beumer JH, et al. A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2006, 840(2):108-115.

1. Yoo CB, Jones PA. Epigenetic therapy of cancer:past, present and future[J]. Nat Rev Drug Discov, 2006, 5(1):37-50.
2. Bolden JE, Peart MJ, Johnstone RW. Anticancer activities of histone deacetylase inhibitors[J]. Nat Rev Drug Discov, 2006, 5(9):769-784.
3. Huang C, Sloan EA, Boerkoel CF. Chromatin remodeling and human disease[J]. Curr Opin Genet Dev, 2003, 13(3):246-252.
4. Shabason JE, Tofilon PJ, Camphausen K. HDAC inhibitors in cancer care[J]. Oncology (Williston Park), 2010, 24(2):180-185.
5. Minucci S, Pelicci PG. Histone deacetylase inhibitors and the promise of epigenetic (and more) treatments for cancer[J]. Nat Rev Cancer, 2006, 6(1):38-51.
6. Duvic M, Vu J. Vorinostat in cutaneous T-cell lymphoma[J]. Drugs Today, 2007, 43(9):585-599.
7. 李虎群, 余聂芳. 组蛋白去乙酰化酶抑制剂抗肿瘤作用机制研究进展[J]. 中国医药指南, 2011, 9(6):47-48.
8. 李晓晖, 李建勋, 李世荣, 等. 环肽类组蛋白去乙酰化酶抑制剂[J]. 化学进展, 2007, 19(5):762-768.
9. Mann BS, Johnson JR, Cohen MH, et al. FDA approval summary:vorinostat for treatment of advanced primary cutaneous T-cell lymphoma[J]. Oncologist, 2007, 12(10):1247-1252.
10. Noh EJ, Lim DS, Jeong G, et al. An HDAC inhibitor, trichostatin A, induces a delay at G2/M transition, slippage of spindle checkpoint, and cell death in a transcription-dependent manner[J]. Biochem Biophys Res Commun, 2009, 378(3):326-331.
11. 楼文珠, 孙雪燕, 李龙珠, 等. 组蛋白脱乙酰酶抑制剂的抗癌作用[J]. 中国细胞生物学学报, 2011(9):1045-1052.
12. Kumagai T, Wakimoto N, Yin D, et al. Histone deacetylase inhibitor, suberoylanilide hydroxamic acid (Vorinostat, SAHA) profoundly inhibits the growth of human pancreatic cancer cells[J]. Int J Cancer, 2007, 121(3):656-665.
13. Crump M, Coiffier B, Jacobsen ED, et al. Phase Ⅱ trial of oral vorinostat (suberoylanilide hydroxamic acid) in relapsed diffuse large-B-cell lymphoma[J]. Ann Oncol, 2008, 19(5):964-969.
14. Vansteenkiste J, Van Cutsem E, Dumez H, et al. Early phase Ⅱ trial of oral vorinostat in relapsed or refractory breast, colorectal, or non-small cell lung cancer[J]. Invest New Drugs, 2008, 26(5):483-488.
15. Blumenschein GJ, Kies MS, Papadimitrakopoulou VA, et al. PhaseⅡtrial of the histone dea cetylase inhibit or vorinostat (Zolinz, suberoylanilide hydroxamic acid, SAHA) in patients with recurrent and/or metastatic head and neck cancer[J]. Invest New Drugs, 2008, 26(1):81-87.
16. 杜晓琅, 朱贺, 丁黎, 等. 液相色谱-串联质谱法同时测定人血清与尿液中伏立诺他及其代谢物4-苯胺基-4-氧代丁酸的浓度[J]. 中国新药与临床杂志, 2012, 31(7):385-391.
17. Du L, Musson DG, Wang AQ. High turbulence liquid chromatography online extraction and tandem mass spectrometry for the simultaneous determination of suberoylanilide hydroxamic acid and its two metabolites in human serum[J]. Rapid Commun Mass Spectrom, 2005, 19(13):1779-1787.
18. Parise RA, Holleran JL, Beumer JH, et al. A liquid chromatography-electrospray ionization tandem mass spectrometric assay for quantitation of the histone deacetylase inhibitor, vorinostat (suberoylanilide hydroxamicacid, SAHA), and its metabolites in human serum[J]. J Chromatogr B Analyt Technol Biomed Life Sci, 2006, 840(2):108-115.

West China Medical Journal

Determination of Vorinostat and M2 Metabolites in Human Serum by High Performance Liquid Chromatography-Mass Spectrometric

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