Determination of Zoledronic Acid and Its Related Substances by High Performance Liquid Chromatography with Evaporative Light Scattering Detection

Abstract

A method has been developed and validated for analysis of zoledronic acid (ZOL) and its related substances by ion-pair reversed-phase high performance liquid chromatography with evaporative light scattering detection (ELSD). Chromatographic separation was achieved with gradient elution by using a C18 column, mobile phase containing 12 mM ammonium acetate buffer and 35 mM n-pentylamine, whose pH value is 7.0, and 5% acetonitrile. The mobile-phase flow rate was 1.0 mL/min. The calibration plot was linear in the range from 0.4 mg/mL to 6.0 mg/mL for ZOL and from 6.25 μg/mL to 100 μg/mL for its related substances. ZOL and its related substances, namely imidazole-1-yl-acetic acid, phosphate, phosphite and degradation products did not interfere with each other. The method was rapid, linear, accurate and reproducible. The high performance liquid chromatographic method that has been developed to determine the related substances and assay of ZOL can be used simultaneously to evaluate the quality of regular samples. It can be also used to test the stability samples of ZOL.

A novel method for determining relative response factors using high‐performance liquid chromatography with photodiode array detector and evaporative light scattering detection

“…HPLC with evaporative light scattering detection (ELSD) can be employed in a wide range of pharmaceutical applications, especially for drugs without UV absorption, 9,10 in the detection of related substances in drugs 11,12 . It has been reported 13 that HPLC with photodiode array detector (PAD) and ELSD can be used to determine the RRFs of drugs that only the volatile buffer mobile phase can separate.…”