Yuzuru Hayashi

Elution of bisphenol-A from hemodialyzers consisting of polycarbonate and polysulfone resins

This study deals with bisphenol-A (BPA) analysis of the BPA-derived polymer pellets, polycarbonate (PC) and polysulfone (PS), and in the hemodialyzer casings made of PC, and the leaching of BPA from commercially available hemodialyzers into water and bovine serum, using HPLC, GC-MS, and LC-MS analyses, and NMR spectroscopy. Total contents of BPA in polymer pellets of each resin were 4.0 and 7.2 microg/g (PC) and 34.5 microg/g (PS). Amounts of BPA released from hemodialyzer PC casings lacking PS hollow-fiber were 11.7 and 13.7 ng/casing by water extraction, and 296 and 345 ng/casing by methanol extraction. On the other hand, BPA of 3.78 to 141.8 ng/module was recovered using water circulation of hemodialyzers, and 140.7 to 2,090 ng/module was detected when bovine serum was used as a circulation solvent. The elution profiles using various concentrations of ethanol/water mixtures indicated that a 17.2% (v/v) ethanol solution rather than bovine serum can be used as an extraction solvent, where a similar amount of BPA as with bovine serum circulation was eluted from the hemodialyzer. Thus, this solvent may be useful for evaluating BPA elution from hemodialyers under similar conditions to medical use.

Modification of the function of mutual information based on information theory and the Kalman filter for chromatographic optimization

Abstract The information measure FUMI (function of mutual information) is used to describe the mutual information of chromatography. In this modified version of FUMI, the mutual information is expressed in terms of Gaussian peak parameters (position of peak maximum, width and area). In an application to liquid chromatography of antipyretics, the modified FUMI is used as a quality criterion for optimization of the binary mobile phase. With the modified version, the mutual information for a multicomponent chromatogram can be interpreted realistically as the difference between two principal elements: (1) the maximal information estimated under conditions where the effect of peak overlap is virtually eliminated; (2) the information loss caused by peak overlap in the actual chromatogram.

Validation of HPLC and GC–MS systems for bisphenol-A leached from hemodialyzers on the basis of FUMI theory

This paper proposes a method for the validation of chromatography systems in which many experiments to estimate SD or RSD are difficult or impossible to carry out because of time, cost, etc. HPLC systems with UV-Vis and fluorescence detectors and GC-MS system for bisphenol-A leached from hemodialyzers are taken as an example. Examined as validation characteristics are not only the ordinary quantities (precision, accuracy, range, limit of detection (LOD), limit of quantitation (LOQ), specificity and linearity) but also precision plots (measurement RSD vs. concentration), 95% confidence intervals of calibration lines and LOD signals over baselines. The precision plots, calibration confidence intervals and LOD signals are shown to be advantageous to validate and compare the analytical performance of the systems. The LOD, LOQ, precision plots and 95% confidence intervals of calibration lines are all derived from the SD of measurements and the reliability of these quantities and plots depends totally on the reliability of the SD estimates. This paper uses a probability theory, called the FUMI theory, to estimate as exact a measurement SD as possible without the replication. The precision of the HPLC and GC-MS systems is shown to coincide with the repeatability obtained by the repetition of measurements.

Probabilistic approach to confidence intervals of linear calibration

It is demonstrated that the statistical reliability of experimentally determined confidence intervals in some linear calibration problems in instrumental analyses can greatly be enhanced if the standard deviation (s, σM) of measurements, which is a theoretical prediction of the instrumental response error, is incorporated into the usual statistical equation instead of the residual of least-squares fitting. The reliability of the calibration depends on not only the fluctuation of calibration lines due to the response error, σM, but also the error of parametrization associated with the a priori response error prediction, i.e., the variance of the response s, Var(σM). The error prediction requires the Fourier transform of an instrumental baseline, signal shape and others (e.g., sample injection error). The variability in the confidence interval from five calibration standards is as small in the probabilistic approach as that for 50 standards in the statistical method. Liquid chromatography and capillary electrophoresis are taken as examples.

A one-dimensional kalman filter for peak resolution

Abstract A one-dimensional Kalman filter algorithm is presented that resolves several overlapped liquid chromatographic peaks without algebraic operations of matrices. The resolving powers or filtering reliability of the algorithm is independent of the number of peaks, but depends on both the peak overlap (resolution value R s ) and the signal-to-noise ratio more significantly than the usual multi-dimensional Kalman filter. The reliability is shown to be similar to that of the multi-dimensional filter for the resolution of overlapped Gaussian peaks with limited R s and S/N values.

Discrimination limit for purity test of human insulin by capillary electrophoresis

Because of the inevitable noise in instrumental analysis, a purity test can overlook an illegitimate drug that contains an undesired substance in a higher amount than the prescribed limit. The lowest (average) amount of undesired substance which leads to the right results of the purity test with 95% probability is referred to here as 95% discrimination limit. This paper presents a method for predicting the discrimination limit for the purity test of human insulin in capillary electrophoresis (CE). The theory and experiments show that if the legitimate limit of a degradation product (desamido insulin) is 3.0% of the total amount of the insulin formulation, the 95% discrimination limit in the CE system used in this study is 3.24% desamido insulin. Since the statistical aspects of the purity test are provided by the interpretation of the baseline fluctuation in the instrument, the usual strategy to repeat the instrumental analysis on the same samples is unnecessary in the present study.

An information theory of chromatography : II. Application of FUMI to the optimization of overlapped chromatograms

Abstract The fu nction of m utual i nformation ( FUMI ) was used as a quality criterion in the optimization of the injection interval in overlapped chromatograms. FUMI , which represents the amount of Shannons mutual information involved in the chromatograms, was calculated for overlapped chromatograms with various injection intervals. The most efficient peak separation was selected with respect to the amount of the mutual information and the observation time. Overlapped chromatograms containing negative peaks were also optimized successfully.

Optimization theory of chromatography

Abstract This tutorial describes the total optimization of a chromatographic process using precision (gF) and efficiency (ϑ) of analysis as criteria. The Shannon mutual information, Φ, describes the precision of chromatographic data. The transmission speed, ϑ, of the information, Φ, through the chromatographic process denotes the efficiency of analysis. The optimum is defined to be the condition that provides the maximal amount of Φ and/or ϑ among all the operating conditions examined. The most precise analysis (the maximum of Φ) and the most efficient analysis (the maximum of ϑ) are demonstrated for the total optimization of six variables, Z (mobile phase composition, wavelength, etc.), in the high-performance liquid chromatographic analysis of an antipyretic mixture. The reliability of these two types of optima is verified by experiments. The analytical roles of the variables are elucidated from the Φ-ϑ plots and the derivatives of Φ and ϑ with respect to Z. Only in cases where the peaks overlap, is an increase in the resolution equivalent to an increase in the mutual information oj for peak j. Conclusions regarding the effects of controllable variables on the optimization are also given.

An information theory of chromatography : I. Evaluation of analytical systems by means of FUMI

Abstract The application of the function of mutual information (FUMI) to the logical evaluation of methods for chromatographic quantitation is described. FUMI provides the Shannon mutual information of overlapped peaks with various resolutions. Hence an analytical method can be evaluated logically based on both the amount of information transmitted by overlapped peaks and the observation period of chromatography. As an example of the evaluation, a previously proposed chromatographic analysis consisting in a rapid but incomplete separation of naphthalene and diphenyl, and peak-deconvolution based on the Kalman filter, is considered. The “best” chromatogram that can transmit the maximal mutual information in unit time is given.

Measurement precision and 1ƒ noise in analytical instruments

Abstract The recently promulgated uncertainty theory of instrumental analyses was used to minimize the relative standard deviation of measurements. Naphthalene, acenaphthene, pyrene and perylene in HPLC were used as illustrations. For a Gaussian model peak with a width (S.D., σ) of fifteen data points, the optimum integration domain was about ±6 data points (±0.4σ) around the peak centre on the HPLC baseline examined. Two commonly used integration modes were examined: horizontal zero line and oblique zero line. The precision was almost the same for both modes in the HPLC analysis. The signal shape at the limit of detection was also shown for the optimum integration domain. The error accompanying the use of the uncertainty theory was evaluated using a Monte Carlo simulation. The practical applicability and limitations of the theory are discussed.