Determination of cationic surfactants as the preservatives in an oral solution and a cosmetic product by capillary electrophoresis

In this study, a capillary electrophoresis method was developed for the determination of cationic surfactants, benzethonium and cetylpyridinium ions, which are commonly used as preservatives in various pharmaceutical and cosmetic products. Determination was performed in a fused-silica capillary using a mixed 75 mmol/L phosphoric acid and 50% acetonitrile electrolyte at pH 2.5. Analysis of benzethonium and cetylpyridinium ions was achieved in around 5 min. Repeatability in migration times (R.S.D.%) for benzethonium and cetylpyridinium ions were 0.3. The calibration curves were linear from 0.0125 to 0.400 mmol/L for benzethonium ions and from 0.025 to 0.400 mmol/L for cetylpyridinium ions. The minimum detection limits (signal-to-noise ratio = 3) are 1.47 and 4.30 μg/mL for benzethonium and cetylpyridinium ions, respectively. The method was applied to the analysis of benzethonium ion in a cosmetic product and cetylpyridinium ion in a mouthwash.     

Potentiometric titration of thiols, cationic surfactants and halides using a solid-state silver-silver sulphide electrode

A rugged, low resistance silver-silver sulphide solid-state electrode for determining pharmaceuticals as authentic samples or in dosage forms by potentiometric titration is described. Sodium tetraphenylborate, mercury(II) acetate and silver nitrate (0.01) M were employed as titrants in the analysis of cationic surfactants (cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride and chlorhexidine salts), antithyroid drugs (methimazole and propylthiouracil) or sodium halides respectively.     

Cetylpyridinium tetrachlorozincate as standard for tenside titration. Analytical methods with 1,3-dibromo-5,5-dimethylhydantoin (DBH) in respect to environmental and economical concern, part 19

The determination of the cationic active disinfectants benzalkonium chloride, benzethonium chloride, cetrimide, and cetylpyridinium chloride according to PH. EUR. 2002 resp. supplement 4.3/2003 can be improved using the DBH-method. By application of column extraction the iodide determination can be performed in the organic layer by visual indication. However, titration in aqueous solution with sodium dodecyl sulphate as titrant and methyl orange resp. bromophenol blue as indicator can be performed more simple. Cetylpyridinium tetrachlorozincate is recommended as a standard for tenside titration.     

Determination of benzalkonium chloride in contact lens solutions by positive-ion fast atom bombardment mass spectrometry

Under positive-ion fast atom bombardment (FAB) mass spectrometric conditions, benzalkonium chloride (BAK) afforded intense peaks at m/z 304 and 332, corresponding to the intact cations [M---Cl]⁺ of C₁₂ and C₁₄ homologues, respectively. The use of benzethonium chloride as an internal standard and thioglycerol as a FAB matrix allowed the direct and specific determination of the BAK content (0.004–0.020%) in commercial hard contact lens solutions through the individual assay of the two alkyl homologues. A linear relationship between the homologue concentration and the peak—area ratio was observed over the concentration range 3–180 μg ml⁻¹.     

Simultaneous identification and quantification by liquid chromatography of benzethonium chloride, methyl paraben and triclosan in commercial products labeled as grapefruit seed extract

A HPLC method has been developed which permits the quantification of methyl paraben, benzethonium chloride and triclosan in various samples of grapefruit seed extract (GSE). The best results were obtained with a Phenomenex Gemini C18 column using gradient mobile phase of water (0.1% acetic acid) and acetonitrile (0.1% acetic acid) with a flow rate of 1.0 mL per minute. The detection wavelength was 254 nm for methyl paraben, and 275 nm for benzethonium chloride and triclosan. The main synthetic antimicrobial agent identified in commercial GSE samples was benzethonium chloride in concentrations from 0.29-21.84%. Positive ion electrospray MS of a commercial GSE sample showed a molecular ion at m/z 412 [M+], which matched that of a standard of benzethonium chloride. Triclosan was detected in two samples at 0.009 and 1.13%concentrations; while methyl paraben was not detected in the samples analyzed.     

HPLC法测定化妆品中防腐剂劳拉氯铵、苄索氯铵和西他氯铵的含量

目的 建立HPLC法测定化妆品中防腐剂劳拉氯铵、苄索氯铵和西他氯铵的含量.方法 采用Agilent Zorbax CN色谱柱,流动相为甲醇-0.1 mol· L-1醋酸铵缓冲溶液(冰醋酸调节pH值至5.0)(75∶25),流速为1.0mL·min-1,检测波长为260 nm,柱温为25℃,进样量为20 μL.结果 劳拉氯铵、苄索氯铵和西他氯铵的检出限分别为0.04 μg,0.07 μg和0.03 μg,线性范围为5.0～100.0 μg·mL-1,回收率为94.4％～102.6％.结论 本研究建立的HPLC方法稳定可靠、简便易行,可用于化妆品中同时测定防腐剂劳拉氯铵、苄索氯铵和西他氯铵的含量,为《化妆品卫生规范》中补充完善禁限用物质检测方法奠定了基础.     

口腔白色念珠菌对西吡氯铵含片的体外溶血活性研究

目的用浓缩漱口水法收集的口咽部念珠菌感染患者的白色念珠菌,检测其是否产生溶血性及西吡氯铵是否对白色念珠菌的溶血活性产生影响。方法收集口腔念珠菌感染的患者的白色念珠菌,经培养、分离、纯化和鉴定后,将其接种于血琼脂平板上,加入西吡氯铵,检测其溶血活性。结果未加入西吡氯铵的对照组的白色念珠菌均产生溶血现象,而实验组（加入西吡氯铵）和阳性对照组（加入氟康唑）的溶血现象明显减少,两者之间无显著性差异（P〉0.05）,两者与对照组相比均有显著性差异（P〈0.05）。结论西吡氯铵能降低白色念珠菌的毒性,可以作为临床上治疗口腔白色念珠菌感染的药物。     

Primary Interactions of Three Quaternary Ammonium Compounds with Blastospores of Candida albicans (MEN Strain)

The absorption of three quaternary ammonium compounds (QAC), cetylpyridinium chloride, cetrimide and benzalkonium chloride, onto the surface of biastospores of Candida albicans (MEN strain) was examined at room temperature. Equilibrium uptake occurred in less than 30 seconds for cetylpyridinium chloride and cetrimide whereas 5 min contact time was required for benzalkonium chloride. The adsorption of all three agents may be mathematically described as Langmuirian and hence a concentration-dependent formation of drug-monolayer on the surface of the blastospore occurred. From this the number of molecules adsorbed onto the surface of a single blastospore was calculated to be 1.33 × 10¹², 3.17 × 10¹² and 2.32 × 10¹² for cetylpyridinium chloride, cetrimide and benzalkonium chloride, respectively. These dissimilarities are most likely due to differences in the orientations of both the cationic nitrogen atom and the accompanying lipophilic portions of each QAC at the blastospore surface. Relating these observations to the known anti-adherence effects of cetylpyridinium chloride and cetrimide, it can be concluded that monolayer coverage of the blastospore surface with QAC does not account for the observed reduced adherence. This suggests that the anti-adherence effects are due to either direct interaction with, or steric blockade of, adhesions on the blastospore surface.     

Influence of cetylpyridinium chloride on corneal permeability to penicillin.

The epithelial surface or the deepithelialized anterior stromal surface of isolated rabbit corneas was perfused for 3 hr with 14C-penicillin in 25 mM Ringer-bicarbonate solution with or without 1% albumin and with or without 0.02% cetylpyridinium chloride. The intact epithelium acted as a barrier to penicillin and impeded the flux rate by 66% when compared to the flux rate across the deepithelialized cornea. The presence of 0.02% cetylpyridinium chloride increased the penicillin flux rate across corneas with an intact epithelial layer to that of deepithelialized corneas. Cetylpyridinium chloride, 0.02%, had no effect on penicillin flux across deepithelialized corneas. The penicillin flux rate across corneas, with or without epithelium, was increased slightly following the inclusion of 1.0% albumin in the bathing solution. The flux rates across deepithelialized corneas in the presence of albumin, with or without cetylpyridinium chloride, were similar to fluxes found in the absence of albumin. Albumin-penicillin "binding" was not a significant factor in impeding penicillin flux, and this binding apparently was not altered by cetylpyridinium chloride. The surfactant appeared to alter epithelial permeability physiologically.     

Silica coatings on clarithromycin

Pre-crystallized clarithromycin (6-O-methylerythromycin A) particles were coated with silica from the tetraethyl orthosilicate (TEOS)-ethanol-aqueous ammonia system. The coatings had a typical thickness of 100-150 nm and presented about 15 wt.% of the silica-drug composite material. The properties of the coatings depended on reactant concentration, temperature and mixing rate and, in particular, on the presence of a cationic surfactant (cetylpyridinium chloride). In the presence of cetylpyridinium chloride the silica coatings slightly decreased the rate of pure clarithromycin dissolution.     

Comparison of cytotoxicity of various surfactants tested on normal human fibroblast cultures using the neutral red test, MTT assay and LDH release.

We used the neutral red test, MTT assay and lactate dehydrogenase (LDH) release to compare the potential cytotoxicity of six surfactants belonging to different classes--three non-ionic surfactants (Triton x100, octylphenoxypolyethoxy alcohol, from Orion; Tween 60, polyoxyethylene (20) sorbitan monostearate, from ICI Speciality Chemicals; Tween 80, polyoxyethylene (20) sorbitan monolaurate, from Labosi), two anionic surfactants (Texapon K1298, sodium lauryl sulphate, from Henkel; Texapon N40, sodium laurylether sulphate, from Henkel) and one cationic surfactant (benzethonium chloride, from Siber Hegner)--on human fibroblast cultures. According to the LC50 (microg ml(-1)), the tested surfactants can be classified in the following order of increasing cytotoxicity: Tween 80 < Texapon N40 < Tween 60 < Texapon K1298 < Triton x100 < benzethonium chloride.     

牙菌斑中氯化十六烷基吡啶含量测定方法学验证

目的建立牙菌斑中氯化十六烷基吡啶(CPC)的测定方法。方法用高效液相色谱-串联质谱法(LC-MS/MS)测定并进行了系统的方法学验证。结果 CPC在浓度为5～100μg.g-1之间,响应值和浓度呈良好的线性关系,线性方程:Y=0.0441X+0.0751,r=0.9951。本方法的定量限(LOQ)为2μg.g-1,检测限(LOD)低于1ng·mL-1。结论表明本方法具有良好的专属性、精密度、重现性和回收率,可应用于牙菌斑中氯化十六烷基吡啶(CPC)的测定。     

Influence of lipophilic counter-ions in combination with phloretin and 6-ketocholestanol on the skin permeation of 5-aminolevulinic acid

In this study, the effect of lipophilic counter-ions on the permeation of 5-aminolevulinic acid (ALA) in combination with skin impregnation by phloretin and 6-ketocholestanol was evaluated. Standard in vitro permeation experiments with porcine skin were performed analysing the ALA content by HPLC and fluorescent detection after ALA derivatisation. The shake flask method in combination with a trinitrobenzensulfonic acid test for ALA analysis was performed to calculate the apparent partition coefficient (logP(Oct)). The permeation of ALA was enhanced by cetylpyridinium chloride and benzalkonium chloride at pH 7.0 and by sodium-1-octanesulfonic acid, sodium-1-heptanesulfonic acid and sodium-1-pentanesulfonic acid monohydrate at pH 4.0. Corresponding effects of these additives were observed on the partitioning of ALA. Pre-impregnation of porcine skin with phloretin and 6-ketocholestanol increased the ALA diffusion about 1.7-fold at pH 7.0. Moreover, this transport enhancement by 6-ketocholestanol was 3.5-fold higher when a combination of ALA and cetylpyridinium chloride was used as donor.     

Studies on the formation of electrostatic complexes between benzethonium chloride and anionic polymers

The chemistry of a mixture of benzethonium chloride and a copolymer of methoxyethylene-maleic anhydride was investigated. This mixture was of interest because it was effective in reducing dental plaque, calculus, and gingival inflammation in vivo. Evidence from dialysis, pH measurements, and stoichiometry demonstrated that the benzethonium cation and the anion of the hydrolyzed copolymer formed an electrostatic complex. An emulsion was produced when a stoichiometric excess of either component was present, but this mixture coacervated at stoichiometric quantities. The stability of the complex was pH dependent, and it did not form in 50% acetone. The complex was decomposed by simulated saliva, mainly due to calcium and magnesium ions, but was unaffected by salivary proteins. Other anionic polymers also formed this type of complex.     

The Effect of Formulation on the Antimicrobial Activity of Cetylpyridinium Chloride in Candy Based Lozenges

Purpose. The purpose of this investigation was to determine the influence on the antimicrobial activity of cetylpyridinium chloride of the various components of the formulation of each of six candy based lozenges. Methods. In vivo activity was investigated using six volunteers by determining the reduction in colony forming units recoverable from the oropharynx after sucking each lozenge separately on different days. In vitro determinations investigated the relative activity of aqueous solutions of the lozenges, the effect on activity of additional active ingredients, pH and lozenge base ingredients against separate inocula of each of the test organisms Staphylococcus aureus, Streptococcus pyogenes and Candida albicans. Results. Both in vivo and in vitro results showed that the pH of the dissolved lozenge solution was the single most influential readily adjustable formulation parameter which significantly influenced the activity of cetylpyridinium chloride activity in candy based lozenges. Conclusions. Lozenges containing cetylpyridinium chloride as the active ingredient should be formulated at a pH greater than 5.5.     

Appraisal of fungistatic and fungicidal activities of quaternary compounds towards yeasts belonging to the genera Candida and Cryptococcus

The fungistatic and fungicidal activities of five quaternary ammonium compounds towards Candida and Cryptococcus strains were determined using a bacteriological method adapted to mycological experiments. It could be deduced from this study that Cryptococcus in spite of the capsule around the cell were more sensitive than Candida and that the benzethonium chloride (BC) exhibited the most effective action against the whole yeasts. No resistance appeared, only Cryptococcus strain was less sensitive than the others.     

西吡氯铵含漱液治疗口腔念珠菌感染的临床疗效分析

目的分析西吡氯铵含漱液治疗口腔念珠菌感染的临床疗效。方法 128例口腔念珠菌感染病患,按照随机方法分为治疗组和对照组,每组64例。两组患者均给予基础的抗菌治疗。对照组选择复方氯己定含漱液施治,治疗组选择西吡氯铵施治。比较两组患者用药前后相关症状(疼痛、红斑、黏膜萎缩)评分及镜检阳性率、治疗效果、用药不良反应发生情况。结果用药后,两组患者的疼痛、红斑、黏膜萎缩评分均低于用药前,且治疗组疼痛、红斑、黏膜萎缩评分均高于对照组,差异具有统计学意义(P<0.05)。治疗组镜检阳性率为6.25%(4/64),对照组镜检阳性率为28.13%(18/64);治疗组镜检阳性率低于对照组,差异具有统计学意义(P<0.05)。治疗组患者的治疗总有效率95.31%高于对照组的78.13%,差异具有统计学意义(P<0.05)。治疗组患者的用药不良反应发生率7.81%(5/64)低于对照组的20.31%(13/64),差异具有统计学意义(χ2=4.137, P<0.05)。结论口腔念珠菌感染选用西吡氯铵含漱液能帮助患者及早控制症状,保障满意临床效果,且具备良好安全性。     

Reaktions-gaschromatographische Bestimmung von Cetylpyridiniumchlorid

Reaction Gas-Chromatographic Determination of Cetylpyridinium Chloride Cetylpyridinium chloride is cleaved to pyridine and cetyl chloride in an injection port at 400°C. By the determination of pyridine and by means of a calibration curve quantitative analyses of aqueous cetylpyridinium chloride solutions in the range of 5000 to 50 ppm can be made.     

硫酸软骨素钠的比浊法测定

建立了硫酸软骨素钠含量的比浊测定法。硫酸软骨素钠与氯化十六烷基吡啶Wong结合形成的乳浊液在680nm处的吸收度与硫酸软骨素钠浓度在12.5-250ug/ml范围内具良好的经性关系,r-0.9992,方法平均回收率为99.98%,RSD为0.33%,乳浊液在0.5-2h内稳定,测定结果与国际常用的HPLC法一致。较国内用的氨基己糖测定法和葡萄糖醛酸测定法简便,重现性好。     

Swelling studies of gelatin. II: Effect of additives

Interactions between gelatin and six cationic, anionic, and nonionic drugs or excipients were investigated through their effects on initial swelling rate and equilibrium swelling of gelatin. Short rectangular strips of Type B gelatin containing the additives were immersed in buffer solutions of pH 7.0 at 20 degrees C. Their weight gain due to uptake of buffer solution and their weight loss due to leaching of the additive and of gelatin were determined as a function of time. During preparation of the strips, methyprylon and dicloxacillin sodium crystallized, while octoxynol 9 separated as small droplets in the gelatin matrix. Up to 7% of gelatin leached into the buffer solution during 96 h of immersion from strips of plain gelatin and strips containing five additives. The sixth additive, cetylpyridinium chloride, tripled the amount of gelatin leached while most of this additive remained in the gelatin strip. The other five additives were largely or completely extracted by the buffer solution. Potassium chloride underwent the fastest leaching, being completely dissolved within the first half hour. Octoxynol 9 was extracted most slowly because the swelling solution formed a viscous liquid crystalline phase inside the gelatin. Swelling followed second-order kinetics. Initial swelling rates and equilibrium swelling were calculated with a linearized function. Cetylpyridinium chloride, dodecylammonium chloride, and methyprylon reduced the initial swelling rate of gelatin while dicloxacillin sodium increased it. Octoxynol 9 and potassium chloride left it unchanged. Cetylpyridinium chloride and dodecylammonium chloride reduced the equilibrium swelling of gelatin substantially. Dicloxacillin sodium and octoxynol 9 increased it substantially, while potassium chloride and methyprylon increased it slightly. The extensive interaction of the cetylpyridinium ion with gelatin may result in reduced bioavailability.