Impurities in drug substance

Presence of specific substances as impurities in drug substances... 

PRESENCE OF SPECIFIC SUBSTANCES AS IMPURITIES IN DRUG SUBSTANCES... 

Impurities in drug substances and drug products continue to be a source of great concern, discussion, debate, and research. " These concerns and debates typically center on the potential safety risks associated with impurities due to contamination and the setting of acceptance criteria. However, the bulk of the work being performed in the pharmaceutical industry, with respect to impurities, is focused on the isolation, identification, qualification and quantification of impurities that are found as a result of the manufacturing process or through chemical decomposition. On the... 

Mol et al. applied MEKC coupled with ESI—MS successfully for the analysis and characterization of impurities in drug substances. 

Organic impurities in drug substance origin, control, and measurement... 

C. Eckers,N. Haskins and J. Langridge.The use of liquid chromatography combined with a quadrupole time-of-flight analyzer for the identification of trace impurities in drug substance. Rapid Communications in Mass Spectrometry, 1997,11(17), 1916-1922. 

The FDA guidance document on impurities in drug substances recommends that individual impurities greater than 0.1% should be fully characterized and quantified by a validated analytical method. In addition, the USP permits up to 2% of ordinary nontoxic impurities in APIs. Such impurities may include residual starting materials, intermediates, reagents, by-products, degradation products, catalysts, heavy metals, electrolytes, filtering aids, and residual solvents. 

FDA. Guidance for Industry, AND As Impurities in Drug Substances (June 1998). 

Nicolas and Scholz, 1998) and ion trap mass (Tiller et al., 1997a) spectrometers have been benchmarked as a routine tool for the characterization of trace impurities in drug substances. 

GUIDANCE FOR INDUSTRY—NDAS IMPURITIES IN DRUG SUBSTANCES 153... 

Generate impurity profile and identify impurities in drug substance and drug product. 

Table 8.1 ICH guidelines for reporting, identification, and qualification thresholds for impurities in drug substances and drug products [7, 8]...

McGovern, T., Jacobson-Kram, D. Regulation of genotoxic and carcinogenic impurities in drug substances and products. Trends Anal. Chem. 25, 790-795 (2006)... 

In general, the detection and identification of impurities present in API and formulations play an integral role in the drug development process and methods need to be developed to adequately resolve these species and quantitate them. The International Conference on Harmonization (ICH) [3] has published a guidehnes on impurities in new drug substances and new drug products (see Table 8-1). The acceptable limit of the impurities in drug substances is dependent upon the maximum daily dose and the quahfication threshold however, lower thresholds are sometimes deemed necessary if the... 

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