title: Simultaneous determination of seven anthraquinones in rat plasma by Ultra High Performance Liquid Chromatography-tandem Mass Spectrometry and pharmacokinetic study after oral administration of Semen Cassiae extract.
abstract: BACKGROUND
  Semen Cassiae, called Juemingzi in China, is the seed of the annual Cassia obtusifolia L., of the leguminosae family. It has been used as healthy drinks to alleviate constipation and improve eyesight for many years in China.
  
  
  OBJECTIVE
  A simple sensitive UHPLC-MS/MS method has been developed and validated for the simultaneous determination and pharmacokinetic study of chrysophanol, emodin, aloe-emodin, rhein, physcion, obtusifolin and aurantio-obtusin in rat plasma.
  
  
  METHODS
  Chromatographic separation was accomplished on a C18 column with a 5min gradient elution. A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) via an electrospray ionization (ESI) source and operating in the negative ionization mode. The samples were prepared by LLE with ethyl acetate after being spiked with an internal standard (butylparaben).
  
  
  RESULTS
  The current UHPLC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The method was linear for all analytes over investigated range with all correlation coefficients greater than 0.9900. The lower limit of quantification (LLOQ) of each analyte was lower than 5ng/mL. Intra-day and inter-day precisions were less than 14.99%. The relative errors of accuracies were in the range of -14.60% to 5.11%. The mean recoveries and matrix effects of anthraquinones were higher than 65.54% and 93.26%, respectively. After oral administration 1.25g/kg of Semen Cassiae extract, the maximum plasma concentration (Cmax) was 1189.25±333.40ng/mL for chrysophanol, 38.48±3.15ng/mL for emodin, 79.20±34.76ng/mL for aloe-emodin, 152.70±23.91ng/mL for rhein, 461.85±266.77ng/mL for physcion, 243.59±22.71ng/mL for obtusifolin and 1950.44±638.86ng/mL for aurantio-obtusin, respectively. The time to reach the maximum plasma concentration (Tmax) was 0.333±0.071h for chrysophanol, 0.333±0.059h for emodin, 0.333±0.009h for aloe-emodin, 0.333±0.09h for rhein, 0.167±0.002h for physcion, 0.5±0.074h for obtusifolin and 0.333±0.06h for aurantio-obtusin, respectively.
  
  
  CONCLUSIONS
  The proposed method was further applied to investigate the pharmacokinetics of seven anthraquinones after oral administration of Semen Cassia extract to rats.
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China.
authors.forename: Chunjuan
authors.initials: C
authors.lastname: Yang
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China.
authors.forename: Shuhong
authors.initials: S
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Guo
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China.
authors.forename: Jiahui
authors.initials: J
authors.lastname: Sun
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.affiliation: College of Pharmacy, Harbin Medical University, 157 Baojian Road, Nangang Distrct., Harbin 150081, PR China. Electronic address: wulijun_111@hotmail.com.
authors.forename: Lijun
authors.initials: L
authors.lastname: Wu
mesh_terms: D000284:Administration, Oral; D000818:Animals; D000880:Anthraquinones / Q000097:blood* / Q000493:pharmacokinetics*; D002366:Cassia / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D008297:Male; D010936:Plant Extracts / Q000008:administration & dosage* / Q000097:blood / Q000737:chemistry* / Q000493:pharmacokinetics; D051381:Rats; D012639:Seeds / Q000737:chemistry; D053719:Tandem Mass Spectrometry
chemical_list: D000880:Anthraquinones; D010936:Plant Extracts
keywords: Anthraquinones; Chrysophanol (PubChem CID:10208); Pharmacokinetics; Rat plasma; Semen Cassiae; UHPLC–MS/MS; aloe-emodin (PubChem CID:10207); aurantio-obtusin (PubChem CID:155011); emodin (PubChem CID:3220); obtusifolin (PubChem CID:3083575); physcion (PubChem CID:10639); rhein (PubChem CID:10168)