ICP-MS: a tool for detection and quantitation of fosfomycin residues in cleaning samples of finished product by estimation of phosphorous load

Abstract

Due to the significance of health risk factors to patients and the requirements imposed by regulatory authorities, the development of a reliable cleaning assessment method holds great importance in the pharmaceutical industry. Reliable, accurate and sensitive analytical techniques are always the need of the hour to establish any cleaning assessment method. Inductively coupled plasma mass spectrometry (ICP-MS) has been acclaimed for its accuracy and sensitivity to detect and analyse trace level elemental toxic metallic impurities. The exploration of using analytical tools to estimate a non-metallic fraction of an organic compound is not very common, especially in cleaning method assessment. This study details using elemental phosphorus in an organic compound as an indirect approach for trace-level analysis in equipment cleaning validation samples. The aim was to determine and quantify trace levels of fosfomycin residue. An analytical method to analyse equipment cleaning samples at a trace level for a fosfomycin tromethamine finished product has not been reported to date. Due to its uniqueness in its structural (non-chromophoric) and physicochemical (acidic) properties, it was a challenging task to develop a sensitive, robust, and rugged cleaning assessment method at a trace level concentration using conventional chromatographic techniques. In order to accomplish this, phosphorus-based quantification using an ICP-MS technique was explored in a rare application. The developed method is benign to the environment, saves time, and is cost effective compared to conventional chromatographic and hyphenated techniques. The developed analytical method was validated as per the principles of ICH guidelines, applicable for the trace-level analysis of equipment cleaning samples. Although the application is specific, the guiding concept can be explored towards analysing other non-chromophoric molecules by optimizing the sample preparation and instrument parameters of the method, e.g., glyphosate (an antibiotic), cisplatin (an anticancer drug), bilanafos (a herbicide), and phosphinothricin (a metabolite of bilanafos).