Effects of different administration methods on the pharmacokinetics and tissue distribution of ribavirin in rats / 中国临床药理学与治疗学

AIM: To establish a HPLC-QqQ-MS with multiple reaction monitoring (MRM) method for pharmacokinetics and tissue distribution study of ribavirin by oral and respiratory administration. METHODS: The experiment established a high-sensitivity LC-MS analytical method for the detection of ribavirin, and the linearity, specificity, recovery, accuracy, and precision were investigated. The established methods were used to investigate the pharmacokinetics and tissue distribution of the oral and respiratory administration methods. RESULTS: The concentration of drugs in the blood through respiratory tract administration is higher, and the drug absorption is faster. Respiratory tract administration C

Analysis of Quality Markers Related to Expelling Phlegm and Arresting Coughing of Trichosanthis Fructus Based Pharmacokinetics and Multivariate Statistical Methods / 中国实验方剂学杂志

Objective:Based on pharmacokinetics， the antitussive and expectorant related quality markers （Q-marker） of Trichosanthis Fructus were screened from diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin， vanillic acid and cinnamic acid， and the candidate Q-marker was evaluated by multivariate statistical method. Method:Six healthy rats were randomly selected and the 70% ethanol extract of Trichosanthis Fructus （dose of 20 g·kg^-1） was given by intragastric administration. Blood was collected from the orbital vein at different time points， and the plasma concentrations of 5 components （diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin， vanillic acid and cinnamic acid） from Trichosanthis Fructus were detected simultaneously by high performance liquid chromatography-triple quadrupole tandem mass spectrometry （HPLC-QqQ-MS/MS）. The main detection conditions were as following：mobile phase of 0.2% formic acid aqueous solution （A）-acetonitrile （B） for gradient elution （0-4 min， 6%-23%B； 4-5 min， 23%-59.5%B； 5-10 min， 59.5%-60%B）， flow rate of 0.5 mL·min^-1， the detection wavelength at 254 nm， electrospray ionization （ESI）， positive ion mode detection， multiple reaction monitoring （MRM） mode scanning， scanning range of <italic>m</italic>/<italic>z</italic> 50-1 500. Diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid with clear pharmacokinetic behaviors were selected as candidate Q-marker about antitussive and expectorant of Trichosanthis Fructus. The contents of these components in 9 batches of medicinal materials were determined and the main detection conditions were the same as the pharmacokinetic study. SPSS 21.0 was used for cluster analysis and principal component analysis （PAC） based on the results of determination. Result:The pharmacokinetic results showed that the area under concentration-time curve （AUC_0-<italic>_t</italic>） of 4 components （diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid） were （111.28±9.94）， （27.08±2.76）， （1 376.12±101.86）， （631.32±64.72） μg·h·L^-1， respectively. The 9 batches of Trichosanthis Fructus samples were clustered into 3 groups by systematic cluster analysis. The clustering results were related to the variety of Trichosanthis Fructus and also affected by the origin. The PCA results showed that the comprehensive scores of Gaotang Trichosanthis Fructus， Shanxi Trichosanthis Fructus， Hebei Ben Trichosanthis Fructus were 1.919， 1.356 and 0.299， respectively， ranking in the top 3 among all samples. The comprehensive scores of Nongkeyuan No. 1， Hebei Trichosanthis Fructus and Nongkeyuan No. 2 were -0.804， -1.085， -1.120， respectively， which were in the last 3 positions among all samples. Conclusion:The pharmacokinetic characteristics and quality evaluation of diosmetin-7-<italic>O</italic>-glucopyranoside， diosmetin， apigenin and vanillic acid meet the requirements about antitussive and expectorant related Q-marker of Trichosanthis Fructus.

Effects of gut microbiota on five absorbed components of Berberis kansuensis in rat serum by HPLC-QqQ-MS / 中国中药杂志

To elucidate the absorption and metabolism of alkaloids in Berberis kansuensis in vivo, a high performance liquid chromatography-triple quadrupole mass spectrometry(HPLC-QqQ-MS) method was developed to qualitatively and quantitatively analyze the absorption components in rat serum in multiple-reaction monitoring mode. The mobile phase consisted of 0.1% formic acid and acetonitrile with a gradient elution mode. In addition, to investigate the effects of gut microbiota on five absorbed components of B. kansuensis in rat serum, diabetic rat and pseudo germ-free diabetic rat models were established, and partial least squares discriminant analysis and One-way ANOVA were used to study the content differences of five components among different groups. In this study, a HPLC-QqQ-MS method for quantitative analysis of five components in rat serum after oral administration of B. kansuensis was established for the first time. It was found that there were differences in the five constituents in rat serum between different groups. By comparing the normal group with the diabetic model group, we found that the absorption and metabolism capacities of berberine and magnoflorine were different under the health and pathological conditions. It was also found that the serum levels of berberine, magnoflorine and jatrorrhizine in pseudo germ-free diabetic rats were significantly lower than those in diabetic rats, indicating that gut microbiota plays an important role in the metabolism of alkaloids of B. kansuensis in vivo. These results provide a good reference for clarifying the active ingredients of B. kansuensis in the treatment of diabetes.

Simultaneous quantification and consistency analysis of 19 representative components in Longshengzhi Capsules by HPLC-QQQ/MS / 中国中药杂志

Longshengzhi capsule consisting of 12 herbs is widely used in clinically treating cerebral ischemia during recovery period.In this study,in order to investigate the consistency of different batches of Longshengzhi capsules,a high performance liquid chromatography coupled to triple quadrupole mass spectrometry method(HPLC-QQQ/MS) was developed for the determination of 19 representative components in Longshengzhi Capsules within 9 min. Methodology validation indicated this method was simple,rapid,accurate,highly sensitive and reproducible,and it could be used for the content determination of components in Longshengzhi Capsules. The consistency analysis results showed that paeoniflorin and calycosin-7-glucoside in Longshengzhi Capsules had the highest content; RSD value of total content of 19 compounds was 5. 2% and the RSD value of main compounds such as astragaloside and calycosin-7-glucoside was all less than 15%,reflecting good consistency among different batches. This study has provided a scientific method and basis for the quality control and consistency evaluation of Longshengzhi Capsules.

Research on concentration of 5 different ginsenosides in Panax japonica collected from different cultivated geographic regions / 中国中药杂志

In this paper, an HPLC-QqQ-MS method for determination of 5 different ginsenosides of Panax japonica collected from different cultivated geographic regions was established. The separation was performed on a Zorbax XDB-C₁₈ (4.6 mm×100 mm, 1.8 μm) column with the gradient elution of acetonitrile (contained 0.1% formic acid)-0.1% formic acid water. The flow rate was 0.5 mL•min⁻¹. The colunm temperature was maintained at 30 ℃. The analytes were detected using electrospray ionization (ESI) in multiple reaction monitoring (MRM) modes. Reaction selected ions were 203.2 for ginsenoside Re, 202.9 for ginsenoside Rg₁, 365.0 for ginsenoside Rf, 789.1 for ginsenoside Rd, 360.9 for ginsenoside Ro. Ginsenosides Re, ginsenosides Rg₁, ginsenosides Rf, ginsenosides Rd, ginsenosides Ro had good linearity in the ranges of 3.33-66.60 μg (r=0.999 1),2.83-56.54 μg (r=0.999 2), 0.32-6.51 μg (r=0.999 2), 12.55-251.00 μg (r=0.999 3), 0.85-16.90 μg (r=0.999 5), respectively. The results of recovery were among 100.8% to 104.6%, and the values of RSD were blow 3.0%. This method is simple, reliable and accurate, and can provide basis for P. japonica basic research.

Comprehensive analysis of chemical constituents in Xingxiong injection by high performance liquid chromatography coupled with mass spectrometry / 中国天然药物

Xingxiong injection (XXI) is a widely used Chinese herbal formula prepared by the folium ginkgo extract and ligustrazine for the treatment of cardiovascular and cerebrovascular diseases. Compared with the pharmacological studies, chemical analysis and quality control studies on this formula are relatively limited. In the present study, a high performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (HPLC-QTOF MS) method was applied to comprehensive analysis of constituents in XXI. According to the fragmentation rules and previous reports, thirty ginkgo flavonoids, four ginkgo terpene lactones, and one alkaloid were identified. A high performance liquid chromatography coupled with triple quadrupole mass spectrometry (HPLC-QQQ MS) method was then applied to quantify ten major constituents in XXI. The method validation results indicated that the developed method had desirable specificity, linearity, precision and accuracy. The total contents of ginkgo flavonoids were about 22.05-25.51 μg·mL(-1) and the ginkgo terpene lactones amounts were about 4.41-8.70 μg·mL(-1) in six batches of XXI samples, respectively. Furthermore, cosine ratio algorithm and distance measurements were employed to evaluate the similarity of XXI samples, and the results demonstrated a high-quality consistency. This work could provide comprehensive information on the quality control of Xingxiong injection, which be helpful in the establishment of a rational quality control standard.

Determination of 12 kinds of pesticide residues in Fritiliariae Thunbergii Bulbus by HPLC-MS / 中草药

Objective: To develop an analysis method based on N-propylethylenediamine (PSA)-HPLC-QQQ-MS/MS for the determination of 12 kinds pesticide residues in Fritiliariae Thunbergii Bulbus and to quantify them in 20 batches of Fritiliariae Thunbergii Bulbus produced in various places in Zhejiang province. Methods: Fritiliariae Thunbergii Bulbus samples were extracted with acetonitrile and purified by the small column of PSA. The prepared samples were analyzed by HPLC-QQQ-MS/MS in multiple reaction monitoring (MRM) mode, and the pesticides were qualitified by the internal standard method. Results: All the 12 pesticides showed good linearities in their reasonable range (r = 0.9986-0.9998), and the average recoveries of all the pesticides were in the range of 68.1%-108.0% at three spiked levels of 90, 300, and 900 ng/mL. The RSD values were in the range of 1.1%-6.1%, and the LODs of each pesticide were all in the range of 0.08-1.0 μg/kg. Conclusion: The method is suitable for the multiresidues analysis of pesticides in Fritiliariae Thunbergii Bulbus simultaneously and the quality of Fritiliariae Thunbergii Bulbus is basically good for the safty although it contains a trace of several pesticide residues.