, Volume 67, Issue 3–4, pp 231–235 | Cite as

LC-MS-MS Determination of Cyclo{(2S)-2-amino-8-[(aminocarbonyl)hydrazono] decanoyl-1-l-tryptophyl-l-isoleucyl-(2R)-2-piperidinecarbonyl} a Novel Histone Deacetylase Inhibitor in Rat Serum

  • Beom Soo Shin
  • Deok Ki Hong
  • Jong Hwan Kwak
  • John Kim
  • Sun Dong Yoo


A rapid and sensitive liquid chromatography-tandem mass spectrometry assay was developed for the determination of a novel histone deacetylase inhibitor, cyclo{(2S)-2-amino-8-[(aminocarbonyl)hydrazono]decanoyl-1-l-tryptophyl-l-isoleucyl-(2R)-2-piperidinecarbonyl} (SD-2007), in rat serum. The mobile phase consisted of acetonitrile and ammonium formate (10 mM) (85:15 v/v), and the flow rate was 0.25 mL min−1. Chromatographic separations were achieved by isocratic elution on a C18 column. Multiple reaction monitoring was based on the transition of m/z = 681.8 → 83.6 for SD-2007 and 372.1 → 176.1 for trazodone (internal standard). A linearity was observed over a concentration range from 2 to 1,000 ng mL−1 (r 2 > 0.999), with the lower limit of quantification at 2 ng mL−1 with 100 μL of rat serum. The mean intra- and inter-day assay accuracy ranged from 98.5–109.7% to 95.2–102.7%, respectively, and the mean intra- and inter-day precision was between 4.3–11.3% and 2.9–13.3%. The developed assay was applied to a pharmacokinetic study of SD-2007 in rats after intravenous injection (dose 4 mg kg−1).


Column liquid chromatography-mass spectrometry LC-MS-MS Pharmacokinetics Histone deacetylase inhibitor SD-2007 


  1. 1.
    Drummond DC, Noble CO, Kirpotin DB, Guo Z, Scott GK, Benz CC (2005) Annu Rev Pharmacol Toxicol 45:495–528CrossRefGoogle Scholar
  2. 2.
    Dokmanovic M, Marks PA (2005) J Cell Biochem 96:293–306CrossRefGoogle Scholar
  3. 3.
    Marks PA, Richon VM, Rifkind RA (2000) J Natl Cancer Inst 92:1210–1216CrossRefGoogle Scholar
  4. 4.
    Krämer OH, Göttlicher M, Heinzel T (2001) Trends Endocrinol Metab 12:294–300CrossRefGoogle Scholar
  5. 5.
    Kouraklis G, Theocharis S (2002) Curr Med Chem Anticancer Agents 2:477–484CrossRefGoogle Scholar
  6. 6.
    Vigushin DM, Coombes RC (2004) Curr Cancer Drug Targets 4:205–218CrossRefGoogle Scholar
  7. 7.
    Mei S, Ho AD, Mahlknecht U (2004) Int J Oncol 25:1509–1519Google Scholar
  8. 8.
    Rasheed WK, Johnstone RW, Prince HM (2007) Expert Opin Investig Drugs 16:659–678CrossRefGoogle Scholar
  9. 9.
    Mai A, Massa S, Rotill D, Cerbara I, Valente S, Pezzi R, Simeoni S, Ragno R (2005) Med Res Rev 25:261–309CrossRefGoogle Scholar
  10. 10.
    Han JW, Ahn SH, Park SH, Wang SY, Bae GU, Seo DW, Kwon HK, Hong S, Lee HY, Lee YW, Lee HW (2000) Cancer Res 60:6068–6074Google Scholar
  11. 11.
    Ueda T, Takai N, Nishida M, Nasu K, Narahara H (2007) Int J Mol Med 19:301–308Google Scholar
  12. 12.
    Lee HY, Jung YH, Han JW, Lee SY, Lee YW, Lee HY, Zee OP, PCT No. WO 02/051846 (2002)Google Scholar
  13. 13.
    Yoo EJ, Lee BM (2007) J Toxicol Environ Health Part A 68:2079–2109Google Scholar
  14. 14.
    Matuszewski BK, Constanzer ML, Chavez-Eng CM (2003) Anal Chem 75:3019–3030CrossRefGoogle Scholar
  15. 15.
    Mei H, Hsieh Y, Nardo C, Xu X, Wang S, Ng K, Korfmacher WA (2003) Rapid Commun Mass Spectrom 17:97–103CrossRefGoogle Scholar
  16. 16.
    Mallet CR, Lu Z, Mazzeo JR (2004) Rapid Commun Mass Spectrom 18:49–58CrossRefGoogle Scholar
  17. 17.
    Shin BS, Kim J, Yoon CH, Kim CH, Park EH, Han JW, Yoo SD (2005) Rapid Commun Mass Spectrom 19:408–414CrossRefGoogle Scholar

Copyright information

© Friedr. Vieweg & Sohn Verlag/GWV Fachverlage GmbH 2007

Authors and Affiliations

  • Beom Soo Shin
    • 1
  • Deok Ki Hong
    • 2
  • Jong Hwan Kwak
    • 2
  • John Kim
    • 3
  • Sun Dong Yoo
    • 2
  1. 1.College of PharmacyCatholic University of DaeguGyeongbukSouth Korea
  2. 2.College of PharmacySungkyunkwan UniversitySuwon, Kyeonggi-doSouth Korea
  3. 3.Clinical ResearchHanmi Pharm. Co. LtdSeoulSouth Korea

Personalised recommendations