吸附溶出伏安法测定普罗帕酮的研究

在pH 6.47的磷酸盐缓冲溶液中,可得到普罗帕酮的吸附溶出峰。峰电位为-1.38V(vs.Ag/AgCl),富集1min,溶出峰电流与普罗帕酮浓度在8.0x10~(-9)～7.0x10~(-7)mol/L范围内呈线性关系。富集4min检测下限为3.0×10(-10)mol/L。该法用于测定普罗帕酮制剂及人血清中的痕量普罗帕酮,均得到了满意的结果,并探讨了电极反应过程机理。     

Improved synthesis of the enantiomers of propafenone using chiral building blocks

Summary A short and efficient synthesis of the enantiomers of the antiarrhythmic drug propafenone (1) is described using both (R)-isopropylideneglycerol tosylate and (S)-glycidyl tosylate as chiral building blocks. The key step of the high yield synthesis is the acetalization of the carbonyl group in 1-(2-hydroxyphenyl)-3-phenyl-1-propanone (2) which allows application of mild reaction conditions in the subsequent alkylation of the phenolic hydroxy group.With our best wishes dedicated to Prof. Dr.H. Achenbach on the occasion of his 65^th birthday     

盐酸普罗帕酮的示波测定

在0.5mol·L -1的NaOH底液中 ,盐酸普罗帕酮在示波计时电位图阴极支产生1个灵敏的切口 ,其二次微分简易示波图上峰高随盐酸普罗帕酮浓度增大而增高 ,可用于定量分析 ;线性范围为2.5×10-6～2.7×10 -5mol·L -1 ,回归方程为h(V)=127.0 +4.48×106c(mol·L -1) ,r=0.9981 ,检出限为1.0×10 -6mol·L-1;对9.000×10-6 mol·L-1 盐酸普罗帕酮5次测定的RSD为2.8 % ,回收率100.6 % ;与高效液相色谱和其他方法相比 ,本法具有仪器简单、方法简便快速、无需通氮除氧等特点。     

A Method for the Synthesis of 2,3-Disubstituted 2,3-Dihydrobenzofurans

Summary.  The synthesis of 2,3-disubstituted 2,3-dihydrobenzofuran diastereomers is described. The key step in the reaction sequence is the chemoselective reduction of a tert. alcohole with tert.-butylamine-borane/AlCl₃. The relative configuration of the substituents on the dihydrofurane moiety was assigned via NMR spectroscopy. Received September 7, 1999. Accepted November 9, 1999     

Effects of modifiers on the chromatographic behaviour of propafenone and its major metabolites

Summary Propafenone (PPF) is a new antiarrhythmic agent with structural features in common with the class of beta-blocking drugs (phenoxypropanolamines). Because of its high lipophilicity, the drug is strongly retained in reverse phase (RP) columns and simultaneous determination with the main polar metabolites 5-OH-PPF, N-depropyl-PPF and 5-OH-4-methoxy-PPF requires long run times (up to 50 min.) Oxidative metabolism in vivo often produces derivatives whose higher polarity results from the addition of a polar group and/or the subtraction of an apolar one. These metabolites show similar chromatographic behaviour in RP mode and the trade-off between their separation and the sensitivity of the parent compound must be investigated. In an effort to shorten the run time we examined the retention of these early eluting substances as a function of different amine additives, pH and organic content in mobile phase using C8 and C-18 columns from different sources, previously characterized for their free silanophilic and hydrophobic activities. Under optimal conditions the run time was reduced to 14 minutes and an application of the optimized method to the determination in plasma samples of the drug and its main metabolites after chronic therapy with PPF is presented. To investigate possible coelution of other yet undiscovered metabolites which could accumulate in some patients under chronic treatment, the analysis was carried out using an electrochemical detection in parallel with the UV. Agreement was found between the two detection procedures and suggest no interference.     

A Simple Method to Measure Plasma Levels of Propafenone with Fluorescence Detection

The aim of the present study was to develop a simple method to measure plasma levels of propafenone by liquid chromatography with a C18 reverse-phase column and fluorescence detection, without previous derivatization of the sample. Linearity was assessed in the range from 50 to 1000 ng mL⁻¹ and had a correlation coefficient of 0.999. The inter- and intra-day coefficients of variation were below 5%. The limits of detection and quantification were 15 ng mL⁻¹ and 50 ng mL⁻¹, respectively. Drug levels were determined satisfactorily in two patients. A simple and reliable method was developed, especially useful in children with heart failure under treatment with propafenone.     

Preparative enantioseparation of propafenone by counter‐current chromatography using di‐n‐butyl l‐tartrate combined with boric acid as the chiral selector

This paper extends the research of the utilization of borate coordination complexes in chiral separation by counter‐current chromatography (CCC). Racemic propafenone was successfully enantioseparated by CCC with di‐n‐butyl l ‐tartrate combined with boric acid as the chiral selector. The two‐phase solvent system was composed of chloroform/ 0.05 mol/L acetate buffer pH 3.4 containing 0.10 mol/L boric acid (1:1, v/v), in which 0.10 mol/L di‐n‐butyl l ‐tartrate was added in the organic phase. The influence of factors in the enantioseparation of propafenone were investigated and optimized. A total of 92 mg of racemic propafenone was completely enantioseparated using high‐speed CCC in a single run, yielding 40–42 mg of (R)‐ and (S)‐propafenone enantiomers with an HPLC purity over 90–95%. The recovery for propafenone enantiomers from fractions of CCC was in the range of 85–90%.