Regulatory Requirement – Validated, Specific, and Stability Indicating Analytical Method for Zoledronic Acid and Its Related Impurities by Ion Pair Reversed Phase Liquid Chromatography (IP-RPLC)

Abstract

A. sensitive and precise ion pair reversed phase liquid chromatographic (IP-HPLC) method was developed and validated for the determination of zoledronic acid in the presence of its impurities and degradants in parental sterile dosage form. The chromatograph employs octadecyl silane chemically bonded to porous silica, stainless steel analytical column with mobile phase of methanol, and buffer at column flow rate of 0.8 mL min⁻¹, temperature thermo stated to 50°C, and a UV-vis detector wavelength of 215 nm. The buffer used in the mobile phase contains phosphate buffer and tetra butyl ammonium hydrogen sulphate as ion pair, and the pH of the buffer adjusted to 7.2 with dilute orthophosphoric acid. The proposed method was established to have sufficient intermediate precision as a similar separation was achieved on another instrument handled by a different operator, and the method was validated for precision, specificity, linearity, range, accuracy, LOQ, ruggedness, and robustness. The method was also successful in the analysis of the drug in marketed samples subjected to stability testing under stressed conditions of pH hydrolysis, oxidation, and temperature stress as per ICH guidelines. Statistical analysis of the data proved that the method is precise and accurate and can be applied for quantification of impurities and actives in pharmaceutical dosage formulation.

Keywords:

• Forced decomposition studies
• ICH
• Stability
• Validation

Notes

^a Per column length.

^b For five replicate injections.

^a (n = 6).

^a (n = 3).