Performance Characteristics of an Ion Chromatographic Method for the Quantitation of Citrate and Phosphate in Pharmaceutical Solutions

Abstract

The performance of an ion chromatographic method for measuring citrate and phosphate in pharmaceutical solutions is evaluated. Performance characteristics examined include accuracy, precision, specificity, response linearity, robustness, and the ability to meet system suitability criteria. In general, the method is found to be robust within reasonable deviations from its specified operating conditions. Analytical accuracy is typically 100 +/- 3%, and short-term precision is not more than 1.5% relative standard deviation. The instrument response is linear over a range of 50% to 150% of the standard preparation target concentrations (12 mg/L for phosphate and 20 mg/L for citrate), and the results obtained using a single-point standard versus a calibration curve are essentially equivalent. A small analytical bias is observed and ascribed to the relative purity of the differing salts, used as raw materials in tested finished products and as reference standards in the analytical method. The assay is specific in that no phosphate or citrate peaks are observed in a variety of method-related solutions and matrix blanks (with and without autoclaving). The assay with manual preparation of the eluents is sensitive to the composition of the eluent in the sense that the eluent must be effectively degassed and protected from CO(2) ingress during use. In order for the assay to perform effectively, extensive system equilibration and conditioning is required. However, a properly conditioned and equilibrated system can be used to test a number of samples via chromatographic runs that include many (> 50) injections.

Preanalytical Quality Evaluation of Citrate Evacuated Blood Collection Tubes—Ultraviolet Molecular Absorption Spectrometry Confronted with Ion Chromatography

“…To exclude additional sources of uncertainty due to different dilution steps, we decided to use the same calibration range for the determination of citrate with HPIC as previously with UV-VIS MAS, which extended from 0.25 to 4 mmol/L. The objectives of DeBorba [8] and Jenke [9], who used ion exchange chromatography for citrate and phosphate determination, differed from ours; no inorganic ions were expected in our case. Ion exchange column AS11 has 600 times lower capacity per column than ion exclusion column ICE-AS1.…”

“…Instrumentation is not so common. Ion exchange chromatography with suppressed conductometric detection was used for citrate determination in pharmaceutical preparations [8,9]. Ion exclusion chromatography separates species on a different principle; strong electrolytes do not reach the ion exchanger due to the Donnan membrane effect, but carboxylic acids pass through, separate, and can be determined with a suppressed conductometric detector [10,11].…”

Bioreductive Dissolution as a Pretreatment for Recalcitrant Rare-Earth Phosphate Minerals Associated with Lateritic Ores

“…Concentrations of total soluble iron were measured using a Dionex ICS-5000 ion chromatography [20] system fitted with an IonPAC CS5A column and an AD25 absorbance detector (Thermo Fisher Scientific Inc.). Phosphate concentrations were measured using a Dionex ICS-5000 ion chromatograph fitted with an Ion Pac AS-11 equipped with a conductivity detector [21]. Concentrations of lanthanum, cerium, uranium, and thorium in filtered (through 0.2 µm pore-sized polycarbonate filters) mineral leachate samples at the end of the experiments were determined by ICP-MS (NexION 300, PerkinElmer, 2015).…”

Analytical Methods for Determination of Counter-ions in Pharmaceutical Salts

“…Several examples of application of IC in the analysis of pharmaceuticals can be found in the recent scientific literature [1][2][3][4][5][6]. A large number of IC col-*Address correspondence to this author at the Omega Laboratory, 11177 Hamon, Montréal, Québec, H3M 3E4, Canada; Tel: 1-514-335-0310, ext.…”