INTRODUCTION
Microbiological assay methods have traditionally been used to quantify the potency, or antimicrobial activity, of antibiotics. These microbiological procedures were historically used to certify antibiotics on a lot-by-lot basis to ensure sufficient activity. Before 1998, monographs for several approved antibiotics were published in FDA’s Code of Federal Regulations, 21 CFR. These regulatory antibiotic assay procedures were later published in USP–NF as the official referee methods to determine the potency of antibiotics. The details of the microbial assay procedures for individual antibiotics, including the challenge organisms and test parameters, are described in Antibiotics—Microbial Assays 〈81〉. Microbial assays provide a direct measure of the effectiveness of the antibiotic against a reference microorganism. Although these microbiological methods have continued to serve as the official compendial referee methods since their publication in USP–NF, many manufacturers have replaced these microbiological analyses with high-performance liquid chromatography (HPLC) methods.
Although the microbiological methods provide direct proof of antimicrobial effectiveness and can integrate all moieties that contribute to antimicrobial effects in a formulation, these methods are less precise, more complex to perform, and slower to complete than alternative methods such as HPLC. Microbial assays also have limited selectivity and are not appropriate for evaluating organic impurities. The specific skill sets required to perform the microbiological antibiotic assays, their unique equipment requirements, and their comparative complexity deter many stakeholders from using these methods.
There are numerous reasons for replacing the microbiological antibiotic assays with chemical assays that use purity or content as surrogates for the measurement of biological activity. The advantages of chemical-based analytical methods have been described previously for simple, single-component antibiotics, as well as complex, multicomponent antibiotics (1). Physicochemical procedures, such as HPLC, allow for simpler preparation and rapid data acquisition with improved precision, accuracy, selectivity, and specificity. HPLC methods can be used effectively for both potency assignment and organic impurity testing. Additionally, because modern instruments and the expertise to use such equipment are widely available, the conversion to alternative methods may be economically advantageous.
This general chapter provides points to consider for manufacturers who want to use physicochemical alternatives instead of the microbial assay methods described in 〈81〉. Given the widespread use of HPLC as an alternative to microbial assay methods, this chapter focuses on HPLC methods. However, the principles set forth in this chapter are applicable to any alternative physicochemical procedure.
Source from USP and Please refer to USP for details:
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