Development and validation of an ion chromatography method for the determination of phosphate-binding of lanthanum carbonate.
Lanthanum carbonate is indicated to reduce serum phosphate in patients with end stage renal disease (ESRD). When given orally, lanthanum carbonate dissociates in the acid environment of the upper gastrointestinal tract to release lanthanum ions. The free lanthanum ions bind with dietary phosphate released from food during digestion to form highly insoluble lanthanum-phosphate complexes which prevent the absorption of phosphate, consequently reduce the serum phosphate. In order to evaluate the in vitro binding capacity of lanthanum carbonate, a simple and efficient ion chromatography (IC) method was developed and validated for determination of phosphate across the pH range encountered in the gastrointestinal tract. Chromatographic separation was achieved on a Dionex ICS-2000 IC system using a Dionex AS16, IonPac (4mmx250mm) analytical column and Dionex AG16, IonPac (4mmx50mm) guard column. Column temperature was maintained at 30 degrees C. Injection volume was 10microL. The compounds were eluted isocratically at a flow rate of 1mL/min and detected by suppressed conductivity. The analytical method was validated according to USP Category I requirements. The validation characteristics included accuracy, precision, quantification limit, linearity, and stability. The intra-day accuracy ranged from 89% to 103% for the solutions of pH 1.2-6.8. The intra-day precision (RSD) ranged from 0.6% to 3.7% for the solutions of pH 1.2-6.8. The analytical range was linear from 2 to 200ppm (mg/L). The R(2) ranged from 0.9998 to 1.0. This method was found to be simple, robust, sensitive, specific, and accurate. It has been successfully applied for determination of phosphate binding to lanthanum carbonate over the human gastrointestinal pH range at different time-points (from 0.5 to 24h).
Samy
Raghu
R
Division of Product Quality Research, Office of Pharmaceutical Science, Food and Drug Administration, Life Science Building 64, 10903 New Hampshire Avenue, Silver Spring, MD 20993, USA.
Faustino
Patrick J
PJ
Adams
Wallace
W
Yu
Lawrence
L
Khan
Mansoor A
MA
Yang
Yongsheng
Y
D002138:Calibration; D002614:Chelating Agents / Q000378:metabolism*; D002852:Chromatography, Ion Exchange / Q000592:standards; D006863:Hydrogen-Ion Concentration; D007811:Lanthanum / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism*; D015203:Reproducibility of Results; D013997:Time Factors
D002614:Chelating Agents; D010710:Phosphates; C119467:lanthanum carbonate; D007811:Lanthanum