﻿Investigating matrix interference in the pharmacopeial limit test for aluminum in citric acid: a re-examination, for revision of the method

Theerasak Rojanarata,Thana Thanayutsiri,Nattapong Yuwansri,Kittithat Maithongdee,Akhayachatra Chinsriwongkul,Sirada Kaewprasert,Noppharat Phadungcharoen

doi:10.3897/pharmacia.69.e78631

Abstract

In many pharmacopoeias, the limit test used for determining the level of aluminum in citric acid labeled for use in the manufacture of dialysate, is based on solvent extraction using 8-hydroxyquinoline and measurement of fluorescence. However, the fluorescence intensity (F.I.) readout from the extract of citric acid samples has been found to be highly dubious, showing low value, and even lower than that of a blank solution. The aim of this work therefore was to examine what effects the matrix has on the test. The comparison of the two standard curves of aluminum solutions in water, against those prepared in citric acid solutions revealed that they differed greatly in terms of slope and y-intercept. In addition, the F.I. values on the plot of the citric acid solution were much lower than that prepared in the water. In another experiment, a decrease in the F.I. of aluminum solution was clearly seen when the co-existing concentration of citric acid was increased. The results inferred that citric acid interfered with the test due to its acidity and metal-chelating capabilities. Based on this evidence, the pharmacopeial limit test for aluminum in citric acid should be revised; otherwise, it could yield results that underestimate aluminum levels and lead to inaccurate conclusions

Highlights

Aluminum contamination of the solutions used in dialysis has been found to cause toxicity such as osteomalacia, anemia, and dementia, in patients suffering from chronic renal failure who undergo long-term dialysis treatment (Parkinson et al 1981; Tsai et al 2018)
Over the range (0–0.06 mg/ml) that covered the concentration of the aluminum standard solution mentioned in the compendial method (0.04 mg/ml), the standard curves obtained from the aluminum solutions prepared in 0.2 g/ml citric acid solution and those prepared in water, differed greatly in terms of both slope and y-intercept (Figure 1), indicating the interference effects caused by citric acid
In which varying concentrations of citric acid were added to 0.04 mg/ml aluminum solutions, a decrease in the F.I. was clearly seen when the co-existing concentration of the citric acid increased (Figure 2)

Summary

Introduction

Aluminum contamination of the solutions used in dialysis has been found to cause toxicity such as osteomalacia, anemia, and dementia, in patients suffering from chronic renal failure who undergo long-term dialysis treatment (Parkinson et al 1981; Tsai et al 2018). In our experience and those reported by other laboratories, F.I. values measured from citric acid samples are low, and even lower than that of a blank solution This can lead to underestimation of the concentration of aluminum and inaccurate conclusions. At the permitted level of aluminum (0.2 ppm), citric acid exists in the sample solution at a much higher concentration than the aluminum analyte (>106 times) In such conditions, it is hypothesized that citric acid may account for the interference, thereby producing unreliable results. It is hypothesized that citric acid may account for the interference, thereby producing unreliable results To test this hypothesis, the effects of the matrix on the compendial test were re-examined in this work by constructing and comparing the standard curves of aluminum solutions without citric acid, with those in which citric acid was. The data are presented as the average of triplicate determinations

Materials and methods

Results and discussion

Conclusion