Determination and pharmacokinetic study of four xanthones in rat plasma after oral administration of Gentianella acuta extract by UHPLC-ESI-MS/MS.

Gentianella acuta (Michx.) Hulten belonging to the family of Gentianaceae is an annual plant mainly distributed in north of China, Mongolia plateau, Siberia and Far East areas of Russia. The whole herb was used as folk medicine to treat hepatitis, jaundice, headache and fever in Mongolia native medicine. Xanthones are the main active compounds of G. acuta and possess a lot of pharmacological and biological activities A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of swertianolin, norswertianolin, bellidifolin and demethylbellidifolin (DMB) in rat plasma after oral administration of G. acuta extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard. LC separation was achieved on an Agilent SB-C18 RRHD column (1.8 μm, 150 mm × 2.1 mm) at 30°C with an isocratic mobile phase consisting of acetonitrile-water (0.1% formic acid) (90:10, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for swertianolin, norswertianolin, bellidifolin, DMB and I.S. were 435.1/272.0, 420.8/258.9, 273.0/258.0, 258.9/214.9 and 193.0/92.0, respectively. The current UHPLC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four xanthones after oral administration of G. acuta extract. The time to reach the maximum plasma concentration (Tmax) was 0.40 ± 0.12 h for swertianolin, 0.27 ± 0.07 h for norswertianolin, 1.00 ± 0.18 h for bellidifolin and 0.94 ± 0.15 h for demethylbellidifolin. The elimination half-time (t1/2) of swertianolin, norswertianolin, bellidifolin and DMB, was 19.7 ± 9.64 h, 11.3 ± 4.51 h, 19.9 ± 8.11 h and 24.9 ± 8.19 h, respectively. This study described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of four xanthones in rat plasma after oral administration of G. acuta extract, and investigated on their pharmacokinetic studies as well.

Wang Z ，Wu Q ，Yu Y ，Yang C ，Jiang H ，Wang Q ，Yang B ，Kuang H ... -  《-》

Determination and pharmacokinetic study of two triterpenoid saponins in rat plasma after oral administration of the extract of Aralia elata leaves by UHPLC-ESI-MS/MS.

Aralia elata (Miq.) Seems (A. elata) grow in Northeast China and the total saponins of A. elata is used to auxiliary treatment for the acute hepatitis, chronic hepatitis and the transaminase on the high side. Aralia-saponinV and Aralia-saponinVI are the major bioactive saponins in A. elata leaves. A selective and sensitive UHPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of Aralia-saponinV and Aralia-saponinVI indwelling the extract in rat plasma in this article. The sample pretreatment involved a one-step extraction of 0.2mL plasma with methanol. Shengmaxinside C was used as internal standard (I.S.). The separation was carried out on an Agilent SB-C18 column (1.8μm, 50mm×2.1mm) at 30°C with a mobile phase of acetonitrile-5mM ammonium acetate (90:10, v/v) at a flow rate of 0.2mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source operating in the negative ionization mode. The optimized mass transition ion-pairs (m/z) monitored for Aralia-saponinV, Aralia-saponinVI and I.S. were 1103.2/941.2, 1119.2/957.0 and 707.0/647.1, respectively. The current UHPLC-MS/MS assay method was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability, and it was suitable for the pharmacokinetic studies of the two saponins after oral administration of extract of A. elata leaves. The lower limits of quantification were 5.70ng/mL for Aralia-saponinV and 6.15ng/mL for Aralia-saponinVI. Intra-day and inter-day precisions were less than 7.4% and the accuracy range was from 1.19% to 8.60%. The mean extraction recoveries of analytes and I.S. from rat plasma were all more than 89.5%. This paper described a simple, sensitive and validated UHPLC-MS/MS method for simultaneous determination of Aralia-saponinV and Aralia-saponinVI in rat plasma after oral administration of the extract of A. elata leaves, and investigated on their pharmacokinetic studies as well.

Wang Z ，Wu Q ，Meng Y ，Sun Y ，Wang Q ，Yang C ，Wang Q ，Yang B ，Kuang H ... -  《-》

LC-MS/MS determination and pharmacokinetic study of four lignan components in rat plasma after oral administration of Acanthopanax sessiliflorus extract.

Acanthopanax sessiliflorus (Rupr. et Maxim.) Seem. is a shrub mainly present in China, Japan and Korea, the root bark of which is considered as one of the sources of Wujiapi and widely used for its various pharmacological effects. A selective and sensitive UPLC-MS/MS method was developed and validated for the determination and pharmacokinetic study of asarinin, sesamin, helioxanthin and savinin in rat plasma. Sample preparation involved a liquid-liquid extraction of the analytes with methyl tert-butyl ether (MTBE). LC separation was achieved on a UPLC C(18) column at 30°C with a mobile phase consisting of methanol-2 mM ammonium acetate (68:32, v/v). The detection was accomplished by multiple-reaction monitoring (MRM) scanning with electrospray ionization (ESI) source operating in the positive ionization mode. The optimized mass transition ion-pairs (m/z) monitored for asarinin, sesamin, helioxanthin, savinin and IS were 372.2/233.0, 372.2/233.0, 349.1/319.0, 352.9/334.9 and 180.0/109.7, respectively. The current LC-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability and was suitable for pharmacokinetic studies of the four lignans after oral administration of Acanthopanax sessiliflorus extract. The time to reach the maximum plasma concentration (T(max)) was 2.50±0.15 h for asarinin, 1.94±0.28 for sesamin, 2.22±0.48 h for helioxanthin and 2.83±0.29 h for savinin. The elimination half-time (t(1/2)) of asarinin, sesamin, helioxanthin and savinin was 6.08±1.10, 11.69±0.50, 7.16±0.52 and 6.26±0.57 h, respectively. This paper described a simple, sensitive and validated UPLC-MS/MS method for simultaneous determination of four lignans in rat plasma after oral administration of Acanthopanax sessiliflorus extract, and investigated on their pharmacokinetic studies as well.

Song Y ，Deng Y ，Huang D ，Wen J ，Liu Z ，Li F ... -  《-》

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 ... -  《-》

UHPLC-ESI-MS/MS determination and pharmacokinetic study of two alkaloid components in rat plasma after oral administration of the extract of Corydalis bungeana Turcz.

Corynoline and acetycorynoline are active compounds of Corydalis bungeana Turcz. with various pharmacological effects such as sedation, anti-leptospira and liver injury protection effects. A specific, simple and sensitive UHPLC-ESI-MS/MS method was developed and validated for the pharmacokinetic study of corynoline and acetycorynoline in rat plasma. Corynoline and acetycorynoline were extracted from plasma samples by liquid-liquid extraction. The analysis was carried out on an Agilent SB-C18 column (1.8 μm, 50 mm×2.1mm) with the mobile phase of acetonitrile-0.1% formic acid (80:20, v/v). The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source in positive mode. The current UHPLC-ESI-MS/MS assay was validated for linearity, intra-day and inter-day precisions, accuracy, extraction recovery and stability. The lower limits of quantification were 0.10 ng/mL for corynoline and 0.353 ng/mL for acetycorynoline. Intra-day and inter-day precision were less than 12.3% and accuracy ranged from 0.18% to 14.9%. The mean extraction recoveries of analytes and internal standard (IS) from rat plasma were all more than 76.2%. This validated method was successfully applied to pharmacokinetic study in rats after oral administration of corynoline, acetycorynoline and the extract of Corydalis bungeana Turcz.

Yang C ，Xiao Y ，Wang Z ，Wang S ，Chen L ，Wu L ，Liu G ... -  《-》