RESUMEN
In addition to degradation products, impurities, and exogenous contaminants, industries such as pharmaceutical, food, and others must concern themselves with leachables. These chemicals can derive from containers and closures or migrate from labels or secondary containers and packaging to make their way into products. Identification and quantification of extractables (potential leachables) and leachables, typically trace level analytes, is a regulatory expectation intended to ensure consumer safety and product fidelity. Mass spectrometry and related techniques have played a significant role in the analysis of extractables and leachables (E&L). This review provides an overview of how mass spectrometry is used for E&L studies, primarily in the context of the pharmaceutical industry. This review includes work flows, examples of how identification and quantification is done, and the importance of orthogonal data from several different detectors. E&L analyses are driven by the need for consumer safety. These studies are expected to expand in existing areas (e.g., food, textiles, toys, etc.) and into new, currently unregulated product areas. Thus, this topic is of interest to audiences beyond just the pharmaceutical and health care industries. Finally, the potential of universal detector approaches used in other areas is suggested as an opportunity to drive E&L research progress in this arguably understudied, under-published realm.
Asunto(s)
Contaminación de Medicamentos , Embalaje de Medicamentos , Espectrometría de Masas/métodos , Embalaje de Medicamentos/instrumentación , Embalaje de Medicamentos/métodos , Humanos , Espectrometría de Masas/instrumentación , Ensayo de Materiales , Preparaciones Farmacéuticas/químicaRESUMEN
Synthesis is described for the haptens 23-demycinosyl-23-deoxy-23-(3-aminoprop-1-yl)-aminotilmicosin (6) from 5-O-mycaminosyltylonolide (OMT) and for 23-demycinosyl-23-deoxy-23-(3-aminoprop-1-yl)-amino-20-dihydrotylosin (10) from demycinosyltylosin (DMT), respectively. The mild reaction conditions used to synthesize the second hapten, DMT derivative 10, were necessary to overcome instabilities and acid lability of DMT. The haptens synthesized here may be further used to produce protein conjugates useful in developing antibodies against the antibiotics tilmicosin and tylosin.
Asunto(s)
Antibacterianos/síntesis química , Haptenos , Macrólidos , Proteínas/administración & dosificación , Tilosina/análogos & derivados , Tilosina/síntesis químicaRESUMEN
The antibacterial properties of macrolide antibiotics (such as erythromycin, tylosin, and narbomycin) depend ultimately on the glycosylation of otherwise inactive polyketide lactones. Among the sugars commonly found in such macrolides are various 6-deoxyhexoses including the 3-dimethylamino sugars mycaminose and desosamine (4-deoxymycaminose). Some macrolides (such as tylosin) possess multiple sugar moieties, whereas others (such as narbomycin) have only single sugar substituents. As patterns of glycosylation markedly influence a macrolide's drug activity, there is considerable interest in the possibility of using combinatorial biosynthesis to generate new pairings of polyketide lactones with sugars, especially 6-deoxyhexoses. Here, we report a successful attempt to alter the aminodeoxyhexose-biosynthetic capacity of Streptomyces fradiae (a producer of tylosin) by importing genes from the narbomycin producer Streptomyces narbonensis. This engineered S. fradiae produced substantial amounts of two potentially useful macrolides that had not previously been obtained by fermentation.