De Ji

Approach based on high-performance liquid chromatography fingerprint coupled with multivariate statistical analysis for the quality evaluation of Gastrodia Rhizoma

Gastrodia Rhizoma is a Traditional Chinese Medicine applied in the treatment of stroke, numbness of limb, headache and dizziness. However, its clinical effect is threatened by sulfur-fumigation used in the process of storage. This article employs content determination coupled with high-performance liquid chromatography fingerprint to investigate the effect of sulfur-fumigation on Gastrodia Rhizoma so as to evaluate the quality of Gastrodia Rhizoma. The result was that most active ingredient in Gastrodia Rhizoma decreased after sulfur-fumigation and the fingerprints analyzed by mathematical statistics between sulfur-fumigated Gastrodia Rhizoma and unfumigated Gastrodia Rhizoma have substantial differences, which reveals that sulfur-fumigation has a significant influence on the quality of Gastrodia Rhizoma. The conclusion of hierarchical clustering analysis, principal component analysis and partial least squares could validate each other, which implies that the method of mathematical statistics applied for assessing the quality of Gastrodia Rhizoma is effective and stable. The method not only affords a viable strategy for distinguishing Gastrodia Rhizoma whether sulfur-fumigated or not and assessment of the quality of Gastrodia Rhizoma, but also provides a reference for other herbal medicine that suffers from sulfur-fumigation.

Pharmacokinetics and liver distribution study of unbound curdione and curcumol in rats by microdialysis coupled with rapid resolution liquid chromatography (RRLC) and tandem mass spectrometry

A sensitive, specific, convenient and endogenous interference-free microdialysis sampling method coupled with RRLC-MS was successfully developed and applied to the determination of protein-unbound curdione and curcumol in biological samples. Microdialysis probes were simultaneously inserted into the jugular vein toward heart and the median lobe near the center of liver of rats under anesthesia. The separation was accomplished on a Zorbax SB-C18 column (2.1 mm × 50 mm, 1.8 μm) with a gradient elution and chromatography was conducted with RRLC system. Analytes were detected by positive ion electrospray tandem mass spectrometry and quantified on the basis of extracted ion chromatography (EIC) peak area signal. The calibration curves were linear over the range of 3.3-213.2 ng/mL for curdione and 8.1-519.2 ng/mL for curcumol. All the validation data, such as accuracy, precision, stability and matrix effect were satisfactory and within the required limits. The validated method was successfully applied to the pharmacokinetic study of curdione and curcumol in rat blood and liver after oral administration of Rhizoma Curcumae extracts. The results could provide a meaningful basis for better understanding of the intracorporal process of Rhizoma Curcumae, which would be helpful for further study both in clinic and laboratory.

Differential pharmacokinetics and the brain distribution of morphine and ephedrine constitutional isomers in rats after oral administration with Keke capsule using rapid‐resolution LC–MS/MS

Opioid and ephedra alkaloids known as the active ingredients for Keke capsule, which is used to treat coughs and bronchial asthma, could have potential adverse effects on the central nervous system. Therefore, an efficient, sensitive rapid-resolution LC-MS/MS method for the simultaneous determination of morphine, ephedrine, and pseudoephedrine in rat plasma and brain tissue homogenate has been developed. The method was validated in the plasma and brain tissue samples, showed good linearity over a wide concentration range (r(2) > 0.99). The intra- and interday assay variability was less than 15% for all analytes, and the accuracy was between -8.8 and 5.7%. The study provided the pharmacokinetics profiles and the brain regional distribution of the three active alkaloids after oral administration of Keke capsule. The results also indicated that significant difference in pharmacokinetics parameters of the epimers was observed between ephedrine and pseudoephedrine.

Comparative pharmacokinetics and tissue distribution of schisandrin, deoxyschisandrin and schisandrin B in rats after combining acupuncture and herb medicine (schisandra chinensis)

Recently, combination therapy with acupuncture and medicine as a practical strategy to treat diseases has gained increasing attention. The present study aimed to investigate whether acupuncture stimulation at ST.36 had a potential impact on the pharmacokinetics and tissue distribution of lignans. An HPLC-ESI/MS analytical method was established and successfully applied to a comparative study of drug concentration in plasma and tissues of three lignans. The parameters area under the plasma concentration-time curve from time zero to the final measurable point and from time zero to infinity, and peak concentration were significantly increased, with a prolonged mean residence time and a corresponding decrease in clearance in comparision with the Schisandra-alone group. Additionally, tissue concentrations of three lignans were improved in the group with acupuncture, especially in liver. The results indicated that acupuncture has a synergistic effect on the pharmacokinetics and tissue distribution of the three lignans, which could postpone their elimination, resulting in a longer blood circulating time in rat plasma and prolonged residence time in target tissues, leading to higher tissue concentration. The findings provide some scientific evidence for the mechanism of the combined use of acupuncture and herbal medicine. Furthermore, we suggest that acupuncture and its combination with herbal medicine should be investigated further as a possible adjuvant therapy in clinical treatment for liver injury.

Analysis of Chemical Variations between Crude and Salt-Processed Anemarrhenae rhizoma Using Ultra-High-Performance Liquid Chromatography–Mass Spectrometry Methods

The present study was designed to systematically investigate the chemical profile differences between crude Anemarrhenae rhizoma (CAR) and salt-processed Anemarrhenae rhizoma (SAR). Ultra-high-performance liquid chromatography–quadrupole time-of-flight mass spectrometry (UHPLC–QTOF-MS), coupled with multivariate statistical analysis was used for the discrimination of chemical profiles and the identification of the differentiation of the chemical constitutions of CAR and SAR. In addition, seven main constituents of CAR and SAR were simultaneously determined by ultra-high-performance liquid chromatography–quadrupole mass spectrometry (UHPLC–MS) for analyzing the content variations. A total of 24 components were found to be the main contributors to the significant difference between CAR and SAR. The structures of the marker compounds were identified based on their chromatographic behaviors, intact precursor ions, and characteristic MS fragmentation patterns. The potential structural transformation mechanism of furostanol saponins during salt processing was explored. The results may provide a scientific foundation for deeply elucidating the processing mechanism of Anemarrhenae rhizoma.

Pharmacokinetic Comparisons of Typical Constituents in Curcumae Rhizoma and Vinegar-Processed Curcumae Rhizoma after Oral Administration to Rats

The Raw Curcumae Rhizoma (R-CR), included in the Chinese Pharmacopoeia Edition 2015, is a well-known Chinese herbal medicine. However, the vinegar-processed Curcumae Rhizoma (V-CR) is used more widely than R-CR. The pharmacokinetics comparison of R-CR and V-CR after oral administration to rats is poorly understood. A novel method, rapid resolution liquid chromatography-tandem mass spectrometry (RRLC-MS) coupled with a sensitive, specific, and convenient microdialysis sampling method, free from endogenous interference was developed in this research. The extracts of R-CR and V-CR were administered orally to each group of rats. The blood and liver microdialysis probes were positioned within the jugular vein toward the right atrium and the median lobe near the center of the liver, respectively. Then, a double-peak phenomenon was observed in the concentration-time curves of curdione in R-CR group, while it was not observed in V-CR group. The liver-to-blood distribution ratio of curdione in V-CR group increased significantly (P < 0.05) compared to that of R-CR group. However, compared with V-CR group, the pharmacokinetic parameters of curcumol exhibited no statistically significant differences from those of R-CR group. These results indicate that vinegar-processed procedure has influence on the pharmacokinetic process of Curcumae Rhizoma in/ns. RRLC-MS coupled with microdialysis system could be used to evaluate the pharmacokinetics of typical constituents in Curcumae Rhizoma after oral administration.

Effects of acupuncture at ST36 on pharmacokinetics of Schisandra lignans in rats

Objective To investigate the influence of acupuncture at ST36 on the pharmacokinetics of Schisandra lignans including schisandrin, deoxyschisandrin and schisandrin B after intragastric administration of Schisandra chinensis (SC) in rats. Methods Twelve male Sprague-Dawley rats were randomly divided into two study groups: SC and SC+acupuncture. Rats in both groups received intragastric SC extract at 5.0 g/kg. Rats in the SC+acupuncture group additionally received acupuncture stimulation at ST36 for 30 min after SC administration. Acupuncture needles were rotated bilaterally for 1 min, left in situ for 20 min, then electrically stimulated for 10 min at 50 Hz frequency and 1–3 mA intensity. A sensitive and specific high performance liquid chromatography electrospray tandem mass spectrometry procedure was developed and validated for simultaneous analysis of three bioactive lignans (schisandrin, deoxyschisandrin and schisandrin B) in rat plasma. Results There were significant differences (p<0.05) between the two study groups in various pharmacokinetic parameters. Area under the plasma concentration–time curve (AUC0–t), area under the plasma concentration–time curve to time infinity (AUC0–∞) and peak plasma concentration (Cmax) for schisandrin, absorption half-life (T1/2α) and AUC0–t for deoxyschisandrin, and Cmax for schisandrin B were increased in the SC+acupuncture group compared with the SC group. T1/2α for schisandrin B only and time to peak concentration (Tmax) for all three lignans were reduced following acupuncture. Conclusions Acupuncture stimulation at ST36 affects the pharmacokinetics of SC in rats. Acupuncture may have a beneficial role in promoting the absorption of lignans from extracts of SC.