New manufacturing processes, more complicated formulations, and increasingly complex global supply chains are just some of the factors making it more difficult for companies to assess and control for impurities in drug substances and drug products.
To ensure patient safety, impurities must be controlled at levels deemed safe. As drug manufacturers develop tests appropriate for their products' impurities, the suitability of their analytical approach must be robust enough to demonstrate consistent and reproducible performance. Adopting impurity reference materials into analytical testing has been shown to enable better identification and control of the amounts of detectable impurities which is imperative to ensure the public safety of medicines. Utilizing impurity materials during early development and validation is growing in importance. USP’s PAIs (Pharmaceutical Analytical Impurities)* are supported by Product Information Sheets with details on identity and purity allowing for enhanced control of drug impurities. The objective of this application note is to illustrate the use of impurity samples – like PAIs – in the development and validation of a Liquid Chromatography (LC) method utilizing a charged aerosol detector (CAD) which is suitable for organic impurities (OI) testing, for Tobramycin, an aminoglycoside antibiotic. The method was developed and validated for Tobramycin free base but could also serve as a starting point for the analysis of Tobramycin sulfate and related drug products.
DOI: https://doi.org/10.31003/USP_AN_PAI_
Tobramycin_Impurity_2023_v1
Background
Due to the low UV absorptivity of tobramycin, and the preference to have a non-derivatization procedure, a HPLC-CAD method was developed by the USP laboratory to analyze Tobramycin and its related compounds. As part of the method development shown here, four impurities (Nebramine, Neamine, Kanamycin B, and Apramycin) were included.
Disclaimer
The following is an application note. It is not a USP standard. Please refer to USP–NF/PF for official monographs and monographs in PF. This app note is intended to serve as a resource for informational purposes only. This document was developed by USP staff without a public comment period and does not reflect USP or USP’s Expert Body opinions of future revisions to official text of the USP–NF. Certain commercial equipment, instruments, or materials may be identified in this document to specify adequately the experimental procedure. Such identification does not imply approval, endorsement, or certification by USP of a particular brand or product, nor does it imply that the equipment, instrument, or material is necessarily the best available for the purpose or that any other brand or product was judged to be unsatisfactory or inadequate. Parties relying on the information in this document bear independent responsibility for awareness of, and compliance with any applicable federal, state, or local laws and requirements.
*Pharmaceutical Analytical Impurities are released using a process developed by USP’s subject matter experts. The release process is based on internal policies, standard operating procedures, and requirements as defined by USP’s Quality Management System. USP is an ISO 9001:2015 certified facility. PAI products are different from official USP Reference Standards. PAI products are not required for compendial compliance.