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Arzneimittelforschung 2012; 62(06): 290-294
DOI: 10.1055/s-0032-1308980
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

Determination of Norcantharidin in Mouse Tissues by Liquid Chromatography Coupled to Tandem Mass Spectrometry and its Tissue Distribution Study

R. Zhang
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
J. Wang
2   Department of Pharmacology Shandong University of Medicine, Jinan, Shandong, PR China
,
G. Yuan
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
C. Wei
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
X. Liu
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
B. Wang
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
H. Gao
3   Department of Health Care, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
,
R. Guo
1   Institute of Clinical Pharmacology, Qilu Hospital of Shandong University, Jinan, Shandong, PR China
› Author Affiliations
Further Information

Publication History

received 13 December 2011

accepted 29 February 2012

Publication Date:
02 April 2012 (online)

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Abstract

The purpose of this study is to determine the concentrations of norcantharidin (CAS NO: 5442-12-6) in mouse tissues and investigate its tissue distribution after intragastric administration of disodium norcantharidate solution. A highly sensitive and specific liquid chromatography-tandem mass spectrometric (LC-MS/MS) method was developed and validated, using ribavirin (CAS NO: 36791-04-5) as the internal standard (IS). Norcantharidin and IS were extracted from 0.3 mL tissue homogenates using protein precipitation with acetone under acid condition. The analyte was separated on a C18 reverse phase column and analyzed by MS/MS in the multiple reaction monitoring (MRM) mode using ESI with positive ionization, m/z 169→123 for norcantharidin and m/z 267→135 for IS. The developed method was validated over a linear range of concentrations 0.01~5 μg·mL − 1 in liver, lung, kidney, stomach, small intestine, uterus and testis, 0.005~0.5 μg·mL − 1 in heart, spleen and brain, the correlation coefficients (r2) were between 0.9918 and 0.9976. The tissue distribution study result was as follows: The AUC0-t of norcantharidin in tissues was in the order as follows: small intestine, stomach, uterus, kidney, testis, liver, lung, spleen, heart, brain.

Key words

norcantharidin - tissue distribution - LC-MS/MS
 

  • References

  • 1 Zheng YL, Shi CL, He YX. Clinical studies on liver cancer of norcantharidin. Hebei Yi Xue 2005; 11: 820-821
    PubMedGoogle Scholar
  • 2 Dong LH, Qu YQ, Liu F et al. Clinical observation on late stage of esophageal carcinoma treated with norcantharidin coupled with radiotherapeutics. Jilin Yi Xue 2002; 5: 301
    PubMedGoogle Scholar
  • 3 An WW, Gong XF, Wang MW et al. Norcantharidin induces apoptosis in HeLa cells through caspase, MAPK, and mitochondrial pathways. Acta Pharmacol Sin 2004; 25: 1502-1508
    PubMedGoogle Scholar
  • 4 An WW, Xue L, Wang MW et al. Apoptosis of L929 cells induced by norcantharidin. China Oncology 2005; 15: 22-25
    PubMedGoogle Scholar
  • 5 Fan YZ, Fu JY, Zhao ZM et al. Effect of norcantharidin on proliferation and invasion of human gallbladder carcinoma GBC-SD cells. World J Gastroenterol 2005; 16: 2431-2437
    PubMedGoogle Scholar
  • 6 Huang XQ, Ling CQ, Song TB et al. Study on Apoptosis of Human Acute T Lymphocyte Leukemia Cell Line 6t-CEM induced by Norcantharidin. Zhejiang Zhong Yi Xue Yuan Xue Bao 2001; 25: 49-52
    PubMedGoogle Scholar
  • 7 Liang FY, Rong Y, Chen L et al. The killing effect and possible mechanism of norcantharidin on mammalian cells. Xi Bei Da Xue Xue Bao (Natural Science Edition) 1999; 29: 262-264
    PubMedGoogle Scholar
  • 8 Massicot F, Dutertre-Catella H, Pham-Huy C et al. In vitro assessment of Renal Toxicity and Inflammatory Events of Two Protein Phosphatase Inhibitors Cantharidin and Norcantharidin. Basic Clin Pharmacol Toxicol 2005; 96: 26-32
    CrossrefPubMedGoogle Scholar
  • 9 Wei CM, Wang BJ, Ma Y et al. Pharmacokinetics and biodistribution of 3H-norcantharidin in mice. Yao Xue Xue Bao 2007; 42: 516-519
    PubMedGoogle Scholar
  • 10 Wei CM, Zhang R, Wang BJ et al. Determination and pharmacokinetic study of norcantharidin in human serum by HPLC-MS/MS method. Biomed Chromatogr 2008; 22: 44-49
    CrossrefPubMedGoogle Scholar