The temperature dependence of the micellisation of chlorpromazine hydrochloride in aqueous solution

The association characteristics of the weakly associating drug chlorpromazine hydrochloride have been examined over the temperature range 10–35 °C by means of conductimetric measurements. Critical micelle concentrations (cmc) have been determined by the application of a recently developed numerical method [Pérez-Rodríguez et al. (1998) Langmuir 14:4422] especially designed for the analysis of the association pattern in highly polydisperse systems of low aggregation number. The cmcs determined in this manner are used in combination with the mass-action model to obtain the thermodynamic parameters of the micellisation process, in particular the surface and hydrophobic contributions to the free energy. The use of exact forms of equations for the thermodynamics of micellisation applicable to systems of low aggregation number leads to values of the enthalpy of micellisation in reasonable agreement with experimentally determined values. Received: 6 January 2000/Accepted: 9 February 2000     

Differential-Pulse Polarographic Determination of Some N-Substituted Phenothiazine Derivatives in Dosage Forms and Urine Through Treatment with Nitrous Acid

 A highly sensitive differential-pulse (DPP) polarographic method is described for the determination of three N-substituted phenothiazine derivatives, chlorpromazine (CZ), promazine (PZ) and promethazine (PMZ). The method involves the use of nitrous acid as an oxidant. Polarographically-active sulphoxides with diffusion-current constants (Id) of 2.53, 3.05 and 3.37 were obtained for CZ, PZ and PMZ, respectively. The polarographic waves were characterized as being diffusion-controlled, irreversible and partly affected by adsorption phenomena. All parameters affecting the oxidation process and polarographic behaviour were optimized and incorporated into the procedure. The limiting current-concentration plots in the DPP mode were rectilinear over the range: 0.006–0.1 mM, 0.005–0.08 mM and 0.008–0.1 mM for CZ, PZ and PMZ, respectively, with minimum detectability (S/N=3) of 3 × 10⁻⁷ M for CZ and PZ, and 4 × 10⁻⁷ M for PMZ, respectively. The kinetic parameters of the electrode reaction, including rate constant, free energy of activation ΔG and effect of temperature on both parameters were studied. The proposed method was successfully applied to the determination of phenothiazines in dosage forms; the results obtained were in agreement with those given with the official methods. The method was further applied to the determination of promazine in spiked human urine. The percentage recovery was 96.86 ± 0.30. The advantages of the proposed method over other reported methods were discussed. A proposal of the electrode reaction was made. Received June 1, 1999. Revision March 10, 2000.     

Ce(Ⅳ)-罗丹明6G化学发光体系与毛细管电泳联用同时测定氯丙嗪和异丙嗪

提出了一种毛细管电泳化学发光联用技术同时测定氯丙嗪和异丙嗪。在酸性条件下,氯丙嗪和异丙嗪能被Ce(Ⅳ)氧化,然后将能量转移给荧光发射体-罗丹明6G,并以化学发光形式释放能量。基于此,结合流动注射技术,以10 mmol/L KH2PO4/H3PO4(pH3.5)为运行缓冲液,实现了两种药物的分离。方法的线性范围分别为4.0×10-8~2.0×10-6g/mL和2.0×10-8~2.0×10-6g/mL,检出限分别为5.6 ng/mL和3.4 ng/mL,对2.0×10-6g/mL异丙嗪平行测定了9次,相对标准偏差为2.8%。方法可用于同时测定人血清中的氯丙嗪和异丙嗪。     

氯丙嗪分子印迹化学发光微流控传感器芯片的研究

以氯丙嗪分子印迹聚合物为识别物质,以鲁米诺-K3Fe(CN)6化学发光体系,建立了一种新型的氯丙嗪化学发光微流控分子印迹传感器芯片的检测方法。利用二氧化碳激光在聚甲基丙烯酸甲酯材质上刻蚀出200μm宽,150μm深的微通道,8 mm长,1 mm宽,0.5 mm深的微检测池。微检测池中填充50μm粒径大小的热聚合得到的氯丙嗪分子印迹聚合物作为识别物质,在线富集氯丙嗪,富集的氯丙嗪可以增强鲁米诺和K3Fe(CN)6的化学发光强度,以化学发光强度定量氯丙嗪量。该传感器的响应值与0.02~0.4μg/mL氯丙嗪呈良好的线性关系,检出限为8 ng/mL(3σ)。该微流控传感器芯片已用于测定人尿液中的氯丙嗪。     

Synchronous fluorescence and UV-vis spectrometric study of the competitive interaction of chlorpromazine hydrochloride and Neutral Red with DNA using chemometrics approaches

In this study, we have shown with the use of UV–vis spectrophotometry and the constant wavelength synchronous fluorescence spectroscopy (CW-SFS) techniques that the pharmaceutical drug, chlorpromazine hydrochloride (CPZ), intercalates into the deoxyribonucleic acid (DNA) double helix by partial exchange with the Neutral Red (NR) molecular probe.

We have also demonstrated that with the use of three-way data plots, it is clear that it is important to have well-defined methodology for the selection of the important CW-SFS method parameter, Δλ. Ad hoc selection of this parameter, or even that based on experience, can readily lead to serious errors, which subsequently can be transferred to the interpretation of results. The said three-way plots provide a straightforward diagrammatic method, which improves the selection process of a satisfactory value for Δλ.

Finally, we used PARAFAC modeling to resolve the complex three-way CW-SFS data, which provided simultaneously the concentration information for the three reaction components, NR, CPZ and NR-DNA, for the system at equilibrium. This PARAFAC analysis indicated that the intercalation of the CPZ molecule into the DNA proceeds by exchanging with the NR probe, and can be attributed to two parallel reactions.     

Phytochemical prospection,evaluation of antibacterial activity and toxicity of extracts of Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz

Libidibia ferrea (Mart. ex Tul.) L.P. Queiroz is a arboreal species found in the Caatinga from Northeast of Brazil that has been used in popular medicine as an anti-inflammatory, healing, analgesic and for the treatment of respiratory system disorders. Therefore, the objective of this work was to evaluate the composition of ethanol extracts from the leaves and inner bark of Libidibia ferrea, as well as to verify its antibacterial activity and as a potential inhibitor of the TetK efflux pump in Staphylococcus aureus strains, in addition to investigating the toxicity of the extracts in a Drosophila melanogaster model. The analysis and quantification of the extracts markers was performed by High Performance Liquid Chromatography (HPLC). To determine the Minimum Inhibitory Concentration (MIC) broth microdilution tests were carried out. The evaluation of efflux pump inhibition was performed by modifying the MIC of antibiotics and ethidium bromide. Mortality and negative geotaxis tests were used to verify the toxicity of extracts on D. melanogaster. Hydrolysable tannins (gallic acid and ellagic acid) and flavonoids were found in HPLC analysis. The extracts did not show antibacterial activity, demonstrating a MIC ≥ 1024 µg/mL, however the ethanolic extract of the leaves decreased the MIC of the antibiotic from 64 µg/mL to 16 µg/mL, but this effect is not associated with the inhibition of the efflux pump. The extracts did not show toxicity in a D. melanogaster model. This is the first study to evaluate the antibacterial activity of L. ferrea extracts on the IS-58 strain of S. aureus, as well as the first to investigate its toxicity using D. melanogaster. From the results, further studies are needed to determine the mechanisms of action of the extract with other antibiotics.     

流动注射光化学荧光法测定药物制剂中的盐酸氯丙嗪

氯丙嗪的流动注射光化学反应在一编结反应器中进行，该反应器盘绕在一荧光灯上并接受由该灯发生出的最大幅波长为３６５ｎｍ的紫外线照射。用２５３．０ｎｍ的激发波长和３７４．５ｎｍ的荧光波长在线测定光化学反应产物的荧光强度。在最佳条件下，检测限为５．４μｇ／Ｌ，采样速度为９０次／ｈ，１ｍｇ／Ｌ的分析物１１次测定的相对标准偏差为０．５％，动态线性范围为０．０１－６．００ｍｇ／Ｌ。所建立的方法已成功地地用于片剂     

A Versatile Method for Determining the Molar Ligand-Membrane Partition Coefficient

A novel method for the quantitative assessment of the membrane partitioning of a ligand from the aqueous phase is described, demonstrated here with the thoroughly studied antipsychotic chlorpromazine (CPZ). More specifically, collisional quenching of the fluorescence of a pyrene labeled fluorescent lipid analog 1-palmitoyl-2[10-(pyren-1-yl)]decanoyl-sn-glycero-3-phosphocholine (PPDPC) by CPZ was utilized, using 1-palmitoyl-2-oleyl-sn-glycero-3-phosphocholine and -serine (POPC and POPS) liposomes as model membranes. The molar partition coefficient is obtained from two series of titrations, one with constant [phospholipid] and increasing [drug] and the other with constant [drug] and varying total [phospholipid], the latter further comprising of large unilamellar vesicles (LUVs) of POPC/POPS/PPDPC at a constant concentration of 10 μM and indicated concentrations of POPC/POPS LUVs. Notably, the approach described is generic and can be employed in screening for the membrane partitioning of compounds, providing that a suitable fluorescence parameter can be incorporated into one population of liposomes utilized as model membranes.