Improved quality control of [18F]fluoromethylcholine.

OBJECTIVES: With respect to the broad application of [(18)F-methyl]fluorocholine (FCH), there is a need for a safe, but also efficient and convenient way for routine quality control of FCH. Therefore, a GC- method should be developed and validated which allows the simultaneous quantitation of all chemical impurities and residual solvents such as acetonitrile, ethanol, dibromomethane and N,N-dimethylaminoethanol. METHODS: Analytical GC has been performed with a GC-capillary column Optima 1701 (50 m×0.32 mm), and a pre-column deactivated capillary column phenyl-Sil (10 m×0.32) in line with a flame ionization detector (FID) was used. The validation includes the following tests: specificity, range, accuracy, linearity, precision, limit of detection (LOD) and limit of quantitation (LOQ) of all listed substances. RESULTS: The described GC method has been successfully used for the quantitation of the listed chemical impurities. The specificity of the GC separation has been proven by demonstrating that the appearing peaks are completely separated from each other and that a resolution R≥1.5 for the separation of the peaks could be achieved. The specified range confirmed that the analytical procedure provides an acceptable degree of linearity, accuracy and precision. For each substance, a range from 2% to 120% of the specification limit could be demonstrated. The corresponding LOD values were determined and were much lower than the specification limits. CONCLUSIONS: An efficient and convenient GC method for the quality control of FCH has been developed and validated which meets all acceptance criteria in terms of linearity, specificity, precision, accuracy, LOD and LOQ.

Development of methodologies for dimethylaminoethanol glycolate assay in association with sunscreens in dermocosmetic formulation

DMAE glycolate (DG) and sunscreens have been used associated in anti-aging dermocosmetic formulations. Despite extensive use of these substances, methods for quantification of DG as raw material and in cosmetic formulations, especially when associated, are not described in the literature. RP-HPLC and non-aqueous titration methods, with determination potentiometric end-point (PT), were developed and validated for rapid assay of DG as raw material and in a topic emulsion in association with sunscreens. Both methods are simple, selective, linear, accurate and precise. The PT method was chosen for stability study of DG in the formulation developed. The proposed formulation presented good stability performance as regards aspect, pH, apparent viscosity, and SPF, with less than 5% of DG degradation compared to initial conditions.

Glicolato de DMAE (DG) e protetores solares têm sido utilizados associados em formulações dermocosméticas antiidade. Apesar da ampla utilização dessas substâncias, métodos de quantificação para DG matéria-prima e em formulações cosméticas, especialmente quando associados, não estão descritos na literatura. Neste trabalho foram desenvolvidas e validadas metodologias por CLAE-FR e titulação em meio não-aquoso, com determinação do ponto final por potenciométrica (TP), para a rápida análise de DG matéria-prima e em emulsão tópica em associação com fotoprotetores. Ambos os métodos são simples, seletivos, lineares, exatos e precisos. O método TP foi escolhido para o estudo da estabilidade do DG na formulação desenvolvida. A formulação proposta apresentou um bom desempenho no que se refere a estabilidade, aspecto, pH, viscosidade aparente e SPF, com menos de 5% degradação do DG comparado as condições iniciais.

Capillary electrophoresis-electrochemiluminescent detection of N,N-dimethyl ethanolamine and its application in impurity profiling and stability investigation of meclophenoxate.

Numerous drugs are carboxylic acid derivatives containing amino group, and hydrolysis reaction of these agents often generates toxic amines. Thus, the detection of amine impurity is of great importance in drug quality control of these amino group-containing ester and amide. A capillary electrophoresis method coupled with end-column electrochemiluminescent detection based on tris(2,2'-bipyridyl)ruthenium(II) system was proposed for the analysis of N,N-dimethyl ethanolamine (DMEA, the degradation product of meclophenoxate) in the presence of its precursor. Baseline separation of DMEA and meclophenoxate can be easily achieved under the selected conditions. DMEA can be assayed within 3 min over the concentration range of 5.0x10(-8) to 3.0x10(-6) mol L(-1) with a detection limit of 2.0x10(-8) mol L(-1) at the signal-to-noise ratio of 3. The relative standard deviations of the signal intensity and the migration time were less than 5.3 and 2.5% for a standard sample containing 1.0x10(-7) mol L(-1) DMEA (n=5), respectively. The presented method has been successfully applied for the profiling of DMEA resulting from the hydrolysis of meclophenoxate in commercial formulations. A primary stability investigation of meclophenoxate in aqueous solution was also carried out at different temperatures, and the results showed that the degradation of meclophenoxate accelerated at the higher temperature.

Quantitative determination of dimethylaminoethanol in cosmetic formulations by nuclear magnetic resonance spectroscopy.

A nuclear magnetic resonance (NMR) spectroscopic method was validated for the quantitative determination of dimethylaminoethanol (DMAE) in cosmetic formulations. The linearity in the range from 0.5000 to 1.5000 g (DMAE salt/mass maleic acid) presents a correlation coefficient > 0.99 for all DMAE salts. The repeatability (intraday), expressed as relative standard deviation, ranged from 1.08 to 1.44% for samples and 1.31 to 1.88% for raw materials. The detection limit and quantitation limit were 0.0017 and 0.0051 g for DMAE, 0.0018 and 0.0054 g for DMAE bitartrate, and 0.0023 and 0.0071 g for DMAE acetamidobenzoate, respectively. The proposed method is simple, precise, and accurate and can be used in the quality control of raw materials and cosmetic gels containing these compounds as active substances.

Is 2-dimethylaminoethanol (deanol) indeed a precursor of brain acetylcholine? A gas chromatographic evaluation.

Acute administration of deanol-p-acetamidobenzoate (Deaner; deanol) has been reported to elevate brain choline (CH) and acetylcholine (ACh) levels. We have developed a specific and sensitive gas chromatographic assay to measure deanol levels in tissue and have applied this assay to our studies of the effect of acute deanol administration on deanol, ACh and Ch levels in rodent brains. Details of the method are described in this text. This procedure is quantitative and yields reproducible results over a wide range of deanol concentrations (0.30-200 nmol). Seven endogenous and pharmacological parameters have been studied using this procedure. In control rodent brain, liver, heart, lung and plasma, we detected no free endogenous deanol (less than 1 nmol/g). After deanol administration, we were able to detect deanol in tissue and have attempted to determine a relationship between these levels and values of ACh in the same tissue. Regardless of deanol pretreatment time (1-30 minutes) or doses (33.3-3000 mg/kg i.p.) used, we detected no increase in mouse whole brain ACh levels. Likewise, there was no detectable elevation in ACh levels in rat whole brain, cortex, striatum or hippocampus after a 15-minute pretreatment with 550 mg/kg of deanol (i.p.). The only elevation in ACh levels which we detected occurred selectively in the striatum of mice pretreated with a massive dose (900 mg/kg i.p.) of deanol for 30 minutes. This selective increase in striatal ACh levels oculd not, however, be related to levels of deanol in the striatum because there was no greater accumulation of deanol in the striatum than in other brain areas tested or in whole brain. These data do not confirm the results of other investigators who reported elevations in whole brain or striatal ACh levels after acute administration of lower doses of deanol. The data emphasize the need for further investigation into the mode of action of deanol and question its suggested role as an immediate precursor of ACh synthesis in the central nervous system.