title: An LC/MS/MS method for simultaneous quantitation of two homoisoflavones: protosappanin B and brazilin with hypoglycemic activity in rat plasma and its application to a comparative pharmacokinetic study in normal and streptozotocin-treated rats.
abstract: BACKGROUND
  The heartwood of Caesalpinia sappan L. (Leguminosae), a widely used Chinese medicine in folk, has been used for the treatment of traumatic injury, stasis pain, amenorrhea, dysmenorrheal, as well as stabbing pain in the chest, abdomen and so on. Protosappanin B and brazilin, as the major bioactive homoisoflavones of Sappan Lignum, are used as the marker components for the quality control of the herb in China Pharmacopoeia.
  
  
  OBJECTIVE
  To establish a sensitive LC/MS/MS method for investigating the pharmacokinetic properties of protosappanin B and brazilin in rats after oral administration of Sappan Lignum extract, and compare their pharmacokinetics difference between normal and streptozotocin-treated rats.
  
  
  METHODS
  A rapid, selective and sensitive LC/MS/MS method was developed and validated for the simultaneous quantification of protosappanin B and brazilin in rat plasma. Normal and streptozotocin-treated rats were orally administered with the Sappan Lignum extract at the same dose of 2.83 g extract/kg body weight (equivalent to 35.56 mg/kg of protosappanin B and 52.25 mg/kg of brazilin), respectively.
  
  
  RESULTS
  After oral administration of Sappan Lignum extract, a remarkable increase (p<0.05) in the value of AUC0-24h, AUC0-∞, Cmax and T1/2 associated with protosappanin B and brazilin was observed in the streptozotocin-treated group. Compared with the normal rats, elimination of both compounds in the streptozotocin-treated rats was slower.
  
  
  CONCLUSIONS
  The established method was successfully applied to compare the pharmacokinetic behaviors of protosappanin B and brazilin in rat plasma after oral administration of Sappan Lignum extract between normal and streptozotocin-treated groups; the results might suggest the accumulation of both compounds in diabetic pathologic states and the adverse reaction should be considered when it was used.
authors.affiliation: Department of Traditional Chinese Medicine, the First Affiliated Hospital of Liaoning Medical University, Jinzhou 121000, China. tong_xz11@126.com
authors.forename: Xiao-Zhe
authors.initials: XZ
authors.lastname: Tong
authors.forename: Hui
authors.initials: H
authors.lastname: Zhu
authors.forename: Yan
authors.initials: Y
authors.lastname: Shi
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Xu
authors.forename: Biao
authors.initials: B
authors.lastname: Wang
authors.forename: Jiu-Han
authors.initials: JH
authors.lastname: Zhao
mesh_terms: D000818:Animals; D019540:Area Under Curve; D001578:Benzopyrans / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D029911:Caesalpinia / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D007887:Fabaceae / Q000378:metabolism; D007004:Hypoglycemic Agents / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007529:Isoflavones / Q000737:chemistry / Q000493:pharmacokinetics* / Q000494:pharmacology*; D008297:Male; D010936:Plant Extracts / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods
chemical_list: D001578:Benzopyrans; D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; D007529:Isoflavones; D010936:Plant Extracts; C044362:brazilin