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 ... -  《-》

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 ... -  《-》

Simultaneous determination of two epimeric furofuran lignans (sesamin and asarinin) of Asarum heterotropoides extract in rat plasma by LC/MS/MS: application to pharmacokinetic study.

A rapid, sensitive and selective liquid chromatography-tandem mass spectrometry was developed to determine two epimeric furofuran lignans (sesamin and asarinin) simultaneously from Asarum heterotropoides extract in rat plasma. Simple protein precipitation with acetonitrile was performed to extract analytes by using alantolactone as an internal standard. Chromatographic separation was achieved using a DIKMA Diamonsil C18 analytical column (4.6 mm × 150 mm, i.d., 5 µm) by isocratically eluting with a mobile phase consisting of methanol/5 mM ammonium acetate/formic acid (75:25:0.1, v/v/v) at a flow rate of 0.8 mL/min. Tandem mass spectrometric detection with an electrospray ionization interface was performed by multiple reaction monitoring in positive ionization mode. This method was validated according to specificity, sensitivity, linearity, intra- and inter-day precision (<10.7%) and accuracy (<2.3%) and recovery and stability in a concentration range of 25.0-15 000 ng/mL for sesamin and 5.00-3 000 ng/mL for asarinin. This method has been successfully applied in a pharmacokinetic study of A. heterotropoides extract containing sesamin and asarinin after this extract was orally administrated in rats.

Ma Y ，Xu K ，Wang S ，Han Y ... -  《-》

Determination and pharmacokinetic study of chiisanogenin in rat plasma by ultra performance liquid chromatography-tandem mass spectrometry.

Chiisanogenin existing in many Acanthopanax species has been reported to possess anti-inflammatory, antibacterial and antiplatelet aggregatory activities. To develop and validate a rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry method for the determination of chiisanogenin in rat plasma and to investigate its pharmacokinetics after oral administration of chiisanogenin or the extract of Acanthopanax sessiliflorus fruits. The sample pretreatment involved a one-step extraction of 0.2 mL plasma with diethyl ether. Acetaminophen was used as the internal standard. The separation was carried out on an ACQUITY UPLC™ BEH C₁₈ column with a mobile phase of acetonitrile-5 mM ammonium acetate (90:10, v/v) at a flow rate of 0.2 mL/min. The detection was performed on a triple quadrupole tandem mass spectrometer by multiple reaction monitoring (MRM) mode via electrospray ionization (ESI) source. A high sample throughput was achieved with an analysis time of 1.1 min per sample. The calibration curve was linear (r² ≥ 0.99) over the concentration range of 5-500 ng/mL with a lower limit of quantification (LLOQ) of 5 ng/mL. The intra-day and inter-day precision (relative standard deviation, R.S.D.) values were below 11% and the accuracy (relative error, R.E.) was within 8% at all three quality control (QC) levels. The method was successfully applied to the pharmacokinetic study of chiisanogenin in rat after oral administration of chiisanogenin and the extract of Acanthopanax sessiliflorus fruits. Other constituents in the extract affected the pharmacokinetic behavior of chiisanogenin.

Yang C ，Yu K ，Song Y ，Qin F ，Li F ... -  《-》

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 ... -  《-》