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Lotus alkaloids fluorescence assay and neferine influence the pharmacokinetics of amiodarone

Author: WanJiaDao
Tutor: WangJiaLing
School: Huazhong University of Science and Technology
Course: Pharmacology
Keywords: Neferine Determination Amiodarone Pharmacokinetics Interaction
CLC: R965
Type: Master's thesis
Year: 2010
Downloads: 35
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Abstract

This paper establishes a new RP-HPLC-FL method for simultaneous determination of three kinds of double lotus hearts benzyl isoquinoline alkaloid content method, and the method and the RP-HPLC-UV comparison. In Hypersil-C18 (250 mm × 4.6mm, 5μm) as stationary phase and methanol - acetonitrile - water - triethylamine (20: 40: 40: 0.12, v / v / v / v) as the mobile phase, detection wavelength and fluorescence detection wavelengths were scanned from the UV and fluorescence scanning to obtain a flow rate of 1.0 mL · min-1. The results showed that three kinds of alkaloids fluorescence excitation and emission spectra of similarity between the respective fluorescence optimum wavelength λex = 280 nm and λem = 620 nm. HPLC-UV and HPLC-FL determination of three kinds of alkaloids, the linear respectively 1 ~ 50μg/mL and 10 ~ 100μg/mL good range of intra-and inter-day RSD values ??of 1.0 to 8.0 percent, plus three alkaloids The recoveries of 95 to 105%. UV detection at the lowest limits of detection and quantification limits were 250 ~ 500 ng / mL and 500 ~ 1000 ng / mL, the lowest detection limit of fluorescence detection and quantification limits were 500 ~ 1000 ng / mL and 1000 ~ 2500 ng / mL. Measured using two different batches detector lotus alkaloids extracted alkaloid content of 3, the results obtained by the two methods show similar levels. This indicates that: lotus hearts three kinds of double-benzyl-isoquinoline alkaloid RP-HPLC-FL detection method is simple, reliable, and accurate, is a new method for the determination of the sample. The second part neferine amiodarone in rat pharmacokinetic studies an impact. Amiodarone small blood sample size determination of the optimal drug concentration on amiodarone (amiodarone) concentrations in biological samples measurement method has been reported in the literature. These methods exist for large sample size or solid phase extraction of biological samples such as consuming relatively large defects. This part is relatively small consuming protein precipitation and liquid - liquid extraction combined approach to the small sample size of biological samples to optimize the determination of amiodarone. This method uses the Agilent 1100 Series HPLC (G1310A advection pump, 20μL loop manual injector, G1314A variable wavelength UV detector, LGC-1025M oven, Sepu3000p chromatography workstation) to Hypersil ODS-C18 ( 4 mm × 10 mm, particle size 10μm) as the stationary phase was methanol - water - acetonitrile - acetic acid (200/36/23.6/0.86, v / v / v / v; pH 7.53) as the mobile phase of acetonitrile precipitation combined methylene chloride extracts and method of sample pretreatment. In our experimental conditions, amiodarone and the internal standard tamoxifen (tamoxifen) have better and better peak separation (R gt; 2), tamoxifen and amiodarone retention time of approximately 8 min and 20 min; 6 SD rats of different sources of impurities in blank plasma samples does not interfere with peaks higher specificity; calculated using the weighted squares good standard curve, the deviation is small, r ≥ 0.99; low, medium, and high The absolute concentrations of amiodarone recoveries in the range of 80-95%, 78-82% recovery of internal standard range; intra-and inter-day precision were less than 9.4% and 10.1%; amiodarone relative recoveries of 96 - 103% range; amiodarone standard on 4 oC placed one month after the residue extracted plasma samples at room temperature to avoid glare placed 12 h, plasma samples at -60 oC in the refrigerator for 1 month and undergone three ice thaw cycles were in stable condition. 2 neferine amiodarone pharmacokinetics in rats of amiodarone (amiodarone), also known as amiodarone, is a commonly used class III antiarrhythmic drugs used clinically to treatment of supraventricular and ventricular arrhythmias. Neferine is extracted from traditional Chinese medicine as a lotus hearts antiarrhythmic active ingredients, our group intends to study amiodarone and neferine of combination therapy. The purpose of this study is to investigate the neferine on the pharmacokinetics of amiodarone. In this study, SD rats were randomly divided into two groups, the first group to study neferine on the pharmacokinetics of oral amiodarone effects; neferine second group for research on the pharmacokinetics of intravenous amiodarone impact. Experiments neferine are used gavage. In the pre-set time point from the orbital venous plexus at the rat blood and immediately centrifuged to obtain plasma removed, frozen at -60 oC in the refrigerator stored until sample analysis. The concentration-time curve obtained amiodarone calculated pharmacokinetic parameters compared between groups using the analysis of variance Cmax and AUC0-96 values. Study found that pretreatment with neferine and were immediately given neferine on the pharmacokinetics of amiodarone had no significant effect. We speculate that the United neferine and amiodarone administration does not need to adjust the dose of amiodarone, but does not require very strict amiodarone plasma concentration monitoring.

Lotus alkaloids fluorescence assay and neferine influence the pharmacokinetics of amiodarone

Abstract

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