A novel device for the determination of liposome/water partition coefficients.

A novel, cheap and easy-to-construct device and a simple method for partition coefficient determination in liposome/water system based on modified equilibrium dialysis have been developed. The device consists of two vials separated by a semi-permeable membrane, through which the free form of a low molecular weight substance is transported by shaking assisted diffusion. Five test substances, eugenol, carvacrol, thymol, 4-hydroxybenzyl alcohol (4-HBA) and butylparaben were analyzed after equilibration in aqueous phase by three methods, HPLC-UV, GC-MS and DPV with comparable results. This shows the possibility of using the proposed method in any laboratory with any equipment capable of analyzing the substance under study. The liposome/water partition coefficients (log Pl/w) determined for eugenol (2.39), thymol (2.83), carvacrol (2.78) and butylparaben (3.30) are consistent with previously published data. A strong effect of NaCl on the liposome/water partition coefficient was observed. The value of log Pl/w = 1.06 determined for 4-HBA in the presence of 0.15 mol L-1 NaCl in the partitioning liposomal system was considerably lower than in the absence of the salt (log Pl/w = 2.06). The developed method was used to determine the partition coefficient of morphine in liposome/water system without NaCl (log Pl/w = 2.65) under given conditions.

Tutorial and spreadsheet for the evaluation of instrumental quantification uncertainty by the linear weighted regression model: Determination of elemental impurities in a nasal spray by ICP-MS.

A tutorial and spreadsheet for the validation and bottom-up uncertainty evaluation of quantifications performed by instrumental methods of analysis based on linear weighted calibrations is presented. The developed tool automatically assesses if calibrator values uncertainty is negligible given instrumental signal precision, assesses signal homoscedasticity by the Levene's test, guides the selection of weighting factors and evaluates the fitness of the regression model to define the calibration curve. The spreadsheet allows the use of the linear weighted regression model without the need for collecting many replicate signals of calibrators and sample by taking previously developed detailed models of signal precision variation in the calibration interval after adjustments to the daily precision conditions. This tool was successfully applied to the determination of the mass concentration of Cd, Pb, As, Hg, Co, V and Ni in a nasal spray by ICP-MS after samples dilution and acidification. The developed uncertainty models were checked through the analysis of nasal sprays after spiking with known analyte concentration levels. The metrological compatibility between estimated and reference analyte levels for 95% or 99% confidence level supports uncertainty model adequacy. The spiked samples were quantified from many replicate signals but uncertainty evaluation from duplicate calibrator and sample signals was assessed by randomly selecting calibrators and sample signals and by numerically defining a minimum acceptable success rate of the compatibility tests. The developed model was proven adequate to quantify the uncertainty of the studied measurements.

Measurement uncertainty evaluation from correlated validation data: Determination of elemental impurities in pharmaceutical products by ICP-MS.

Pharmaceutical products as well as active pharmaceutical ingredients (APIs) are checked for levels of elemental contaminants to guarantee medicines administration will not involve the consumption of level of contaminants greater than their maximum admissible intake. However, the conformity decision is affected by the measurement uncertainty function of analytical steps performance, used standards quality and how measurement performance is assessed during method validation. When an ingredient is considered conform, since the measured concentration is lower than the maximum limit, the risk of a false acceptance depends on how close the measured concentration is from the limit and on the measurement uncertainty. The analytical methods used for pharmaceutical analysis should be validated by ICH and USP recommendations, in order to prove measurements are fit for purpose. The validation must also be economically feasible and have an acceptable duration. This work discusses how to evaluate the uncertainty of elemental analysis in pharmaceutical ingredients from data collected during the validation of the analytical method by following ICH guidelines and USP chapters. A top-down uncertainty evaluation based on results from the analysis of a model API intermediate, with the native analyte after spiking at three concentration levels, where analyses are performed by two analysts in two different days, is presented. The impact of the correlation of some uncertainty components of collected results on the uncertainty evaluation is discussed and considered in the calculations. The developed measurement model was checked by a cross-validation procedure where some validation data was randomly removed and used for an independent model control. The developed uncertainty evaluation methodology was successfully applied to the analysis of Pd in a model API intermediate by ICP-MS after a micro-wave assisted acid digestion, where the risk of a false acceptance of the pharmaceuticals is determined. The measurement performance data and used spreadsheet are made available as Supplementary Material.

A novel fused-silica capillary dropping mercury electrode with long drop-time and its application on determination of critical micelle concentration.

A novel long drop time mercury electrode has been constructed from common fused-silica capillary (50 µm I.D., 360 µm E.D.). Proposed device provides reproducible mercury drops with typical lifetime 40-120 s. The electrode was used for a set of electrocapillary measurements aimed at determination of critical micelle concentration of anionic surfactants by a convection controlled drop-time technique. A critical micelle concentration of sodium dodecyl sulfate 5.6 ± 0.4 mmol L(-1) and 4.3 ± 0.4 mmol L(-1) were obtained in 1 mmol L(-1) and 5 mmol L(-1) phosphate buffer (pH 7.0), respectively. The values were comparable to those obtained from conductometric measurements under the same conditions (7.0 ± 0.1 mmol L(-1) and 5.2 ± 0.1 mmol L(-1), respectively) and the difference was explained in accordance with theory of hemi-micelle formation.