RESUMO
Objective: To describe the pharmacokinetic profile of Yuanhu Zhitong Tablet (YZT) when administered to Beagle's dogs, a simple and sensitive method for determining tetrahydropalmatine and imperatorin in plasma of dogs was developed and validated by liquid chromatography tandem mass spectrometry (LC-MS/MS). Methods: Plasma samples were treated by a liquid-liquid extraction method with methyl tertiary butyl ether. Etofesalamide was used as internal standard (IS). The separation was performed on a ZORBAX Eclipse XDB-C18 column (50 mm × 4.6 mm, 5 μm) at 40 ℃ with a flow rate of 0.4 mL/min using gradient mobile phase. The mobile phase was consisted with methanol and 0.1% formic acid in water. After separated by liquid chromatography, analytes and IS were detected in electrospray ionization source (ESI) positive ion mode at the specific multiple reaction monitoring (MRM) transitions of m/z 356.2 [M + H]+→m/z 192.1 for tetrahydropalmatine, m/z 271.1 [M + H]+→m/z 203.0 for imperatorin, and m/z 258.1 [M + H]+→m/z 121.1 for IS. The pharmacokinetic parameters for tetrahydropalmatine and imperatorin were calculated by WinNonlin 6.3 pharmacokinetic program using non-compartmental analysis. Results: Good linearity was achieved over the concentration ranges of 0.05-20 ng/mL for tetrahydropalmatine and 0.005-2 ng/mL for imperatorin, with the lower quantification limit of 0.05 and 0.005 ng/mL, respectively. The intra-and inter-batch precisions were less than 14.4%, and the accuracies were within ± 7.19% for all analytes. The mean extraction recoveries of analytes were between 88.2%-107%, and the matrix effects of analytes were between 82.2%-108%. The pharmacokinetic parameters of tetrahydropalmatine after ig administration of YZT including tmax, Cmax, AUC0~t, AUC0~∞, MRT0~t, MRT0~∞, Vd, CL, and t1/2 were as follows: (1.08 ± 0.20) h, (48.70 ±18.10) ng/mL, (170.00 ± 75.70) h·ng/mL, (178.00 ± 77.50) h·ng/mL, (6.41 ± 1.13) h, (8.09 ± 1.85) h, (133.00 ± 63.00) L, (11.90 ± 5.54) L/h, and (7.71 ± 1.07) h; The pharmacokinetic parameters of imperatorin were (1.17 ± 0.26) h, (0.063 4 ± 0.023 5) ng/mL, (0.1760 ± 0.091 9) h·ng/mL, (0.204 0 ± 0.097 3) h·ng/mL, (2.550 ± 0.669) h, (3.640 ± 0.818) h, (22 351 ± 7 990) L, (7 917 ± 6 030) L/h, and (2.390 ± 0.877) h. Conclusion: The fully validated LC-MS/MS method is successfully applied to a pharmacokinetic study on tetrahydropalmatine and imperatorin in Beagle's dogs following ig administration of YZT.
RESUMO
Objective: To clarify the rationality and to provide reasonable usage references of processed Corydalis Rhizoma (CR) in clinic by comparing respectively pharmacological actions including analgesic, anti-inflammation, antiplatelet aggregation and spasmolysis of Yuanhu Zhitong Tablet (YZT) and Yanhusuo Decoction (YD) constituted with raw CR (RCR) or processed CR (PCR). Methods: The hot-board, acetic-acid-induced twisting experiments and mouse auricular swelling model by injecting xylene in the abdomen of mouse were adopted to investigate the analgesic and anti-inflammatory effects of the four formulas on Kunming mice; The experiment of contractile activity on isolated rat intestine smooth muscle on Wistar rats was applied to observing the spasmolysis effect of the four formulas; The experiments of platelet aggregation induced by ADP or collagen on Wistar rats by turbidimetry method were used to observe the anti-platelet aggregation effect of the four formulas. Results: Compared with RCR in two prescriptions, PCR displayed better analgesic effect (P < 0.05, 0.01), while there was no difference on anti-inflammatory effect; Inhibition of the two prescriptions on smooth muscle spasm was presented well, and the prescription YD with PCR was remarkable (P < 0.05, 0.01); Compared with the blank group, the two prescriptions showed outstanding effects on anti-platelet aggregation (P < 0.01), but no difference between RCR and PCR in two prescriptions. Conclusion: PCR can improve the analgesic effect of prescription YZT and intensify the spasmolysis effect of prescription YD, which can be explained by the Chinese medicine processing regulation. Therefore, PCR is suggested to be chosen in YZT and YD used to cure pain symptoms.
RESUMO
A quality control (QC) strategy for quantitative and qualitative analysis of “common peaks” in chemical fingerprint was proposed to analyze Yuanhu Zhitong tablet (YZT), using high performance liquid chromatography with diode array detector and tandem mass spectrometry (HPLC-DAD-MS/MS). The chromatographic separation was achieved on an Agilent Eclipse plus C18 column with a gradient elution using a mixture of 0.4‰ ammonium acetate aqueous (pH 6.0 adjusted with glacial acetic acid) and acetonitrile. In chemical fingerprint, 40 peaks were assigned as the “common peaks”. For quantification of “common peaks”, the detection wavelength was set at 254 nm, 270 nm, 280 nm and 345 nm, respectively. The method was validated and good results were obtained to simultaneously determine 10 analytes (protopine, jatrorrhizine, coptisine, palmatine, berberine, xanthotoxin, bergapten, tetrahydropalmatine, imperatorin and isoimperatorin). For qualification of “common peaks”, 33 compounds including 10 quantitative analytes were identified or tentatively characterized using LC-MS/MS. These results demonstrated that the present approach may be a powerful and useful tool to tackle the complex quality issue of YZT.
RESUMO
OBJECTIVE:To establish capillary electrophoresis method for the determination of imperatorin and isoimperatorin in Yuanhu zhitong tablet. METHODS:The separation was performed on a uncoated fused silica capillary (55 cm?75 ?m ID,effective length of 47 cm) with 20 mmol?L-1 NaH2PO4+100 mmol?L-1 SDS+80%formamide as buffer solution (pH=7.12). The separation voltage was 15 kV and the sample was injected by gravity (5 s,15 cm). The detection wavelength was 254 nm. RESULTS:The linear range of imperatorin and isoimperatorin were 8.0～40.0 ?g?mL-1(r=0.998 7) and 4.0～20.0 ?g?mL-1(r=0.999 0). The average recovery was 101.3% for imperatorin (RSD=3.24%,n=6) and 100.2% for isoimperatorin(RSD=1.44%,n=6). CONCLUSION:The method is convenient,rapid and accurate for the quality control of Yuanhu zhitong tablet.
RESUMO
Objective: To study the preparation and quality control methods of Yuanhu Zhitong HBS Tablet. Methods: the suitable excipients and formulation process of Yuanhu Zhitong HBS Tablet is sieved by means of testing quantity of tetrahydropalmatine through TLC UV. Results: the beginning floating time of HBS Tablet is 3min; relative dissolution of main component tetrahydropalmatine is 32% within 3hr, 86% within 9 hr. Conclusions: the study is found to be effective in the process of Yuanhu Zhitong HBS Tablet.