Model studies on multiple channel analysis of free magnesium

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Anal. Chem. 1985, 57,2647-2651

2647

Model Studies on Multiple Channel Analysis of Free Magnesium, Calcium, Sodium, and Potassium at Physiological Concentration Levels with Ion-Selective Electrodes Matthias Otto' and J. D. R. Thomas*

Department of Applied Chemistry, U W I S T , P.O. Box 13, Cardiff CFl 3XF, Wales, United Kingdom

Simultaneous analysls of free metal ion concentrations with ion-seiectlve electrodes ( ISEs) may be achleved even for nonspeclfic sensors. Thls Is demonstrated for the determlnatlon of Caz+, Mg2+, K+, and Na+ ions at concentratlons typical of Intracellular, urine, or serum levels based on calibrations wlth standards of mixtures of the metal Ions rather than just single metal Ion containing soiutlons. The advantages of data reduction by means of partial least squares (PLS) In prlncipal components compared to ordinary least squares (OLS) anaiysls are outlined. By use of additlonai sensors for one analyte (overdetermlned systems) and the PLS algortthm for data reduction, calclum and magnesium can be analyzed even when present at slmiiar concentrations with mean errors of less than 7%.

Analysis of several components in mixtures by means of nonspecific sensors has been demonstrated in infrared (I) and ultraviolet (1,2) spectrometry, in spectrofluorometry ( 3 , 4 ) , and for unresolved peaks in gas (5) and liquid (6) chromatography. Ion-selective electrodes (ISEs) are also nonspecific sensors since, normally, they respond in varying degrees to other ions rather than specifically to a single ion. ISEs may be successfully used for various samples, especially body or intracellular fluids, but problems can arise if the compositions of samples are such that certain ionic components interfere with the ISE being used. One way of overcoming such interference is the development of more specific sensors, but another possibility, considered here, is calibration of the ISEs with respect to all ions that interfere with the determination of the primary ion. Such an approach is essentially a multicomponent analysis which need not be restricted to conventional ISEs and might also become an attractive tool when chemical-sensitive field-effect transistor (ChemFET) integrated-circuit sensors are commercially available. The simultaneous on-line measurement of blood K+, Ca2+, and Na+ ions and pH with a quadruple-function ChemFET by Sibbald, Covington, and Carter (7) is encouraging with respect to ISE-type multiple channel determinations. However, since ion-selective ChemFET sensors (ISFETs) are fabricated from essentially the same membrane materials as conventional ISEs, the problems caused by limited selectivity, apply to ISFETs as much as to conventional ISEs. Techniques for calibration and data reduction of ISE measurements that enable simultaneous analysis of ions even in the case of nonspecific drifting and noisy sensors are described in this paper. The techniques are illustrated for determinations of ionized K+, Na+, Mg2+,and Ca2+ions under conditions typically found in blood serum, urine, or single cells. The most difficult problem is to determine Mg2+ions in the 'Present address: De artment of Chemistry, Bergakademie Freiberg, 9200 Freiberg GbR.

presence of similar concentrations of Ca2+ions with a magnesium ISE that lacks selectivity toward Mg2+ions with respect to calcium. This is overcome by measuring the ion concentrations with more sensors than analytes to be determined combined with multiple regression analysis based on partial least squares (PLS) rather than the ordinary least squares (OLS) solution. The electrodes used for demonstrating the principles involved are commercially available glass membrane type for sodium, valinomycin type for potassium, and Phillips plastic IS561 for calcium, and laboratory-made electrodes for calcium and magnesium. These provide model systems, and the principles described below for solution systems to illustrate samples of various ranges of ionic compositions might also be applied to other electrode types, such as, microelectrodes. Also, of course, there are many other ISE types for the ions chosen here; especially those recently discussed in an excellent review on neutral carrier based ISEs by Simon and co-workers (8). These frequently have membrane compositions to fit different types of applications, e.g., ionized Ca2+in blood and microelectrodes for intracellular Ca2+activity measurements (8).

EXPERIMENTAL SECTION Apparatus. Emf measurements were carried out with a Radiometer Model PHM64 pH-millivolt meter. The ISEs were interconnected to the meter via a switch that allowed sequential sampling of emf data measured at 25 "C relative to a saturated calomel electrode. The digitized emf values were used for data analysis on a VAX 11/780 computer. Electrodes. For sensing Na+, K', and Ca2+ ions a glass membrane sodium ISE (EIL Analytical Instruments, No. 1048200), a valinomycin-type potassium ISE (Philips No. 9436-09475261), and the Philips commercial plastic IS561 calcium ISE (No. 9436-094-75861),respectively, were used. Ca2+ions were also measured with an ISE made of calcium bis(di[4-(1,1,3,3-tetramethylbutyl)phenyl]phosphate)sensor (DTMBPP) immobilized in PVC in the presence of di-n-octylphenylphosphonate mediator (DOPP), while Mg2+ions were determined with an electrode based on the same (DTMBPP) sensor mixed with solvent mediators of just decan-1-01 or of mixtures of DOPP/decan-1-01 at ratios of 1:l (v/v) as previously described (9). For measurements of Ca2+ ion concentrations M, the calcium ISEs were conditioned in M CaZt ion solutions. Reagents. All chemicals were of analytical reagent grade unless specified. For the adjustment of free Ca2+ion concentrations