Benzoylhypaconitine/(1α,6α,10α,13α,14α,15α,16β,17ξ)-8,13,15-Trihydroxy-1,6,16-trimethoxy-4-(methoxymethyl)-20-methylaconitan-14-yl benzoate/Benzoylmesaconine/Aconitane-8,13,14,15-tetrol, 1,6,16-trimethoxy-4-(methoxymethyl)-20-methyl-, 14-benzoate, (1α,6α,10α,13α,14α,15α,16β,17ξ)-/Benzoylhypacoitine
Methanol; Ethanol; Chloroform
663.6±55.0 °C at 760 mmHg
HS Code Reference
Personal Projective Equipment
For Reference Standard and R&D, Not for Human Use Directly.
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A new enzyme-linked immunosorbent assay (ELISA) method for quantitative determination of monoester-type aconitic alkaloids was developed. The antibodies derived from the immunogen of benzoylmesaconine (BM) could be electively affined to benzoylaconitine-type alkaloids with an ester bond (14-benzoyl-), especially to benzoylhypaconine (BH, 140.02% of cross-reactivity). The effective working range of BH was 1 ng/ml to 5 μg/ml; the lower limit of detection and the quantification were 0.35 and 0.97 ng/ml, respectively. The values of CV for intra-day and inter-day assays and recovery ratios were in acceptable ranges. The results of stability experiments were also satisfactory. This validated method was employed for pharmacokinetic study of BH in rats and the bioavailability orally administered was estimated to be 16.3%.
Enzyme-linked immunosorbent assay (ELISA); antibodies; benzoylhypaconine; benzoylmesaconine; bioavailability
An enzyme-linked immunosorbent assay for monoester-type aconitic alkaloids and its application in the pharmacokinetic study of benzoylhypaconine in rats.
Liu CC1, Xu YH1, Yuan S1, Xu Y1, Hua ML1.
A rapid, specific and sensitive liquid chromatography-tandem mass spectrometry (LC/MS/MS) method was developed for simultaneous quantitation of six Aconitum alkaloids, i.e. aconitine (AC), mesaconitine (MA), hypaconitine (HA), benzoylaconine (BAC), benzoylmesaconine (BMA) and benzoylhypaconine (BHA) in human plasma collected from 18 healthy volunteers after intravenous drop infusion of “SHEN-FU” injectable powder in three different dosages. Lappaconitine was selected as the internal standard (IS). LC/MS/MS system coupled with an electrospray ionization (ESI) source was performed in multiple-reaction monitoring (MRM) mode. The transitions of the Aconitum alkaloids executed as following: m/z 646.3–>586.0 for AC; m/z 632.4–>573.1 for MA; m/z 616.2–>556.1 for HA; m/z 604.2–>104.8 for BAC; m/z 590.1–>104.8 for BMA; m/z 574.1–>104.8 for BHA; m/z 585.2–>161.8 for IS. Sample preparation was performed with solid-phase extraction (SPE) on a 1 mL HLB cartridge prior to analysis. The separation was applied on a Waters C(18) column (1.7 microm, 2.1 mm x 100 mm) and a gradient elution of methanol and 0.1% formic acid-water was used as mobile phase. The retention time was less than 4.5 min. The concentrations ranged from 0.1 to 1000 ng/mL for all six Aconitum alkaloids and showed a good linearity with the correlation coefficient (r(2)) >0.995. The validated method was employed to simultaneous quantitation and successfully used for the first time for the pharmacokinetic evaluation of the six Aconitum alkaloids after intravenous drop administration of “SHEN-FU” injectable powder in phase I clinical trial.
Simultaneous quantitation of aconitine, mesaconitine, hypaconitine, benzoylaconine, benzoylmesaconine and benzoylhypaconine in human plasma by liquid chromatography-tandem mass spectrometry and pharmacokinetics evaluation of "SHEN-FU" injectable powder.
Zhang F1, Tang MH, Chen LJ, Li R, Wang XH, Duan JG, Zhao X, Wei YQ.
2008 Oct 1
A rapid and sensitive high-performance liquid chromatography-mass spectrometric (HPLC-MS) method was developed and validated for simultaneous determination of benzoylhypaconine (BHA), benzoylmesaconine (BMA), benzoylaconine (BAC) and hypaconitine (HA) in rat plasma for the first time. The analytes were separated on a Kromasil C₁₈ column with a total running time of 11 min. The validation data demonstrated a sound feasibility for the newly developed method and it was then applied to the pharmacokinetic study of these analytes in rats. Pharmacokinetic behaviors of BHA, BMA, BAC and HA in rats were studied after oral administration of Radix Aconiti Lateralis Praeparata extract (FZ) and Dahuang Fuzi Decoction (DFD). The main parameters for the two groups of subjects were compared, and significant differences between Radix Aconiti Lateralis Praeparata extract group and Dahuang Fuzi Decoction group in calculated parameters, such as the area under the plasma concentration-time from zero to the last quantifiable time-point (AUC(₀-t)), the area under the plasma concentration-time curve from zero to infinity (AUC(₀-∞)), peak plasma concentration (C(max)), half-life of elimination (T₁/₂), mean retention time (MRT(₀-t)), plasma clearance (CL), volume of distribution (V(d)) and time to reach Cmax (T(max)), were found. After oral administration of DFD, the AUC(₀-t), AUC(₀-∞) and C(max) of BHA, BMA, BAC and HA decreased remarkably (p < 0.05) compared with those of the FZ extract group. Vd and CL values of BHA, BMA, BAC and HA increased, two of which showed significant difference (p < 0.05). T₁/₂ and MRT(₀-t) values of BHA, BMA and BAC in the DFD group were significantly delayed compared with those of FZ extract group. Only the T(max) of HA, the toxic ingredient in FZ, delayed significantly in DFD group compared with the value of FZ group. All these pharmacokinetic parameters were statistically compared, and the rationality of the combination for DFD was clearly demonstrated.
Copyright © 2013 John Wiley & Sons, Ltd.
LC-MS; benzoylaconine; benzoylhypaconine; benzoylmesaconine; hypaconitine; pharmacokinetic
Comparative pharmacokinetics studies of benzoylhypaconine, benzoylmesaconine, benzoylaconine and hypaconitine in rats by LC-MS method after administration of Radix Aconiti Lateralis Praeparata extract and Dahuang Fuzi Decoction.
Liu X1, Li H, Song X, Qin K, Guo H, Wu L, Cai H, Cai B.