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.

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. 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. 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). 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. The proposed method was further applied to investigate the pharmacokinetics of seven anthraquinones after oral administration of Semen Cassia extract to rats.

Yang C ，Wang S ，Guo X ，Sun J ，Liu L ，Wu L ... -  《-》

Simultaneous determination of aurantio-obtusin, chrysoobtusin, obtusin and 1-desmethylobtusin in rat plasma by UHPLC-MS/MS.

A sensitive and reliable ultra-high-performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-MS/MS) method was developed and validated for the simultaneous determination of four active components of Semen Cassiae extract (aurantio-obtusin, chrysoobtusin, obtusin and 1-desmethylobtusin) in rat plasma after oral administration. Chromatographic separation was achieved on an Agilent Poroshell 120 C18 column with gradient elution using a mobile phase that consisted of acetonitrile-ammonium acetate in water (30 mm) at a flow rate of 0.4 mL/min. Detection was performed by a triple-quadrupole tandem mass spectrometer in multiple reaction monitoring mode. The calibration curve was linear over a range of 3.24-1296 ng/mL for aurantio-obtusin, 0.77-618 ng/mL for chrysoobtusin, 34.55-1818 ng/mL for obtusin and 1.86-1485 ng/mL for 1-desmethylobtusin. Inter- and intra-day assay variation was <15%. All analytes were shown to be stable during all sample storage and analysis procedures.

Zhang WD ，Wang PY ，Wang Y ，Wang Q ，Gu Y ，Cao J ，Wang SQ ，Wang XJ ... -  《-》

Simultaneous Determination of Seven Anthraquinone Aglycones of Crude and Processed Semen Cassiae Extracts in Rat Plasma by UPLC-MS/MS and Its Application to a Comparative Pharmacokinetic Study.

Guo R ，Wu H ，Yu X ，Xu M ，Zhang X ，Tang L ，Wang Z ... -  《MOLECULES》

Development of an UHPLC-MS/MS method for comparative pharmacokinetics of nine anthraquinones in rats and application to dosage conversion between different Semen Cassiae forms.

Semen Cassiae, called Juemingzi in Chinese, is widely used in clinic for alleviating constipation, improving eyesight and preventing hyperlipidemia. It can be used as medicine or food including many application forms, such as traditional pieces and ultrafine granular powder (UGP). In this paper, comparative pharmacokinetics of Semen Cassiae in different forms of traditional pieces and UGP were achieved to research the clinical dosage of UGP. Also, the scientific connotation of brewing way for traditional pieces of Semen Cassiae application in clinic was revealed. To achieve this purpose, a rapid, sensitive and reliable UHPLC-MS/MS method was developed for simultaneous determination of rhein, emodin, aloe-emodin, chrysophanol, physcion, aurantio-obtusin, chryso-obtusin, obtusifolin and obtusin in rat plasma. Multiple reaction monitoring mode via an electrospray ionization was applied for the quantitation of the analytes. The separation was carried out on an Agilent Extend-C18 column (100 mm × 2.1 mm, 1.8 μm) with an 8.0 min gradient elution using ultra-purify water and acetonitrile as mobile phase. The samples were prepared by liquid-liquid extraction with ethyl acetate. The development and validation of bioanalytical method were performed according to the latest "Bioanalytical Method Validation: Guidance for Industry" issued by FDA in 2018. Finally, the clinical dosage of UGP was concluded to be 1/4 of Semen Cassiae traditional pieces in oral administration way by comparing the pharmacokinetic parameters of UGP to that of traditional pieces in the aspect of mathematical statics using plus of AUC values.

Xie L ，Liu X ，Zhu X ，Xu Y ，Peng S ，Sun K ，Cai H ，Dai Q ，Wang C ，Zhou Q ，Cai B ... -  《-》

Simultaneous Determination of Purpurin, Munjistin and Mollugin in Rat Plasma by Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry: Application to a Pharmacokinetic Study after Oral Administration of Rubia cordifolia L. Extract.

Gao M ，Yang J ，Wang Z ，Yang B ，Kuang H ，Liu L ，Wang L ，Yang C ... -  《MOLECULES》