Tetracyclines stability

Tetracycline has a secondary binding site in the H27 switch region that may also be fimctionally significant. The dtug binds at the interface of the three domains of 16S rRNA, close to helix 44 and between helices 11 and 27. As with the primary binding site, contacts are made from the hydrophilic face of the dtug to the backbone of 16S rRNA. In this binding site, tetracycline may function to stabilize the ram state. 

The operational stability of the IME was determined by the performance of the IME in a real cellulose hydrolysis reactor. 50-mL tubes were charged with 2.5 g a-cellulose (50 g/L) in 10 mM sodium acetate pH 4.8. Tetracycline and cycloheximide... 

He found the order of stability for several drugs in sugar syrup and honey were as follows sulfa drugs > streptomycin > tetracycline > chlortetracycline > erythromycin > oxytetracycline. 

Tetracycline antibiotics are generally considered relatively unstable compounds. Oxytetracycline posseses limited stability in aqueous solutions and shows specific and base catalysis, with overall hydrolysis observed to follow pseudo-first-order kinetics. The maximum stability of this drug is exhibited at pH 2, whereas the optimum stability ranges from pH 1 to 3, which accounts for the recent finding (70) that oxytetracycline has greater heat stability at pH 3 than at pH 6.9. 

Tetracyclines have the tendency to form chelates with bivalent metal ions. As a consequence of their affinity to calcium, tetracyclines tend to accumulate in the bones of treated animals. Although their chelates with calcium show considerable stability, tetracyclines can be extracted from bones containing these drugs and, therefore, may be present in soups and meals when bones from treated animals are cooked (80, 81). The extractability of chlortetracycline from bone tissue is strongly pH-dependent, being higher at low pH values. This can be easily explained by the dependence of the dissociation constant of the chelate from the pH value. 

Due to their extremely polar character, tetracyclines bind with proteins to form conjugates that are difficult to extract from biological matrices. Use of dilute mineral acids is of great help in dissociating tetracyclines from proteins, but once in aqueous solution, their exfraction into volatile organic solvents for further concentration and cleanup is hampered by the unfavorable partition coefficients. Most of these antibiotics are photosensitive compounds, whereas all of them show poor stability under strong acidic and alkaline conditions with reversible formation of the 4-epi-tetracyclines in weakly acidic conditions (pH 3), and anhydro-tetracyclines in strong acidic conditions (below pH 2). 

Burger, A. and Ratz, A.W. (1990). Physical and chemical stability of amorphous and crystalline tetracycline hydrochloride,Sci. Pharm., 58 69-75. 

This system is advantageous since tetR has high specificity for both its operator sequences and tetracycline (Hillen and Wissmann, 1989 Takahashi et al., 1986). This allows the system to function at tetracycline concentrations well below toxic levels in mammalian cells (Gossen et al., 1995). Tetracycline-derivatives, such as doxycycline, have been shown to be even better inducers than tetracycline. This is due to their increased affinity for tetR and high functional stability (Gossen et al., 1995 Gossen and Bujard, 1993). This system is commonly referred to as Tet-off since the gene is turned off in the presence of tetracycline. 

The choice of the mobile phase is very important, as fluorescence is sensitive to fluorescence quenchers. Highly polar solvents, buffers, and halide ions quench fluorescence. The pH of the mobile phase is also important to fluorescence efficiency for example, quinine and quinidine only display fluorescence in strongly acidic conditions, whereas oxybarbiturates are only fluorescent in a strongly alkaline solution [67,68]. Due to the stability of the chromatographic sorbents, the use of very acidic or basic mobile phase may not be possible. One alternative is to alter the effluent pH postcolumn. Postcolumn addition of sulfuric acid has been used for the assay of ethynodiol diacetate and mestranol in tablets [69]. Another example is the determination of tetracycline antibiotics in capsules and syrup where EDTA and calcium chloride were added to enhance fluorescence [70]. 

Diluents, although commonly presumed inert, do have the ability to influence the stability or bioavailability of the dosage form. For example, dibasic calcium phosphate (both anhydrous and dihydrate forms) is the most common inorganic salt used as a filler-binder for direct compression. It is particularly useful in vitamin products as a source of both calcium and phosphorous. Milled material is typically used in wet-granulated or roller-compacted formulations. The coarse-grade material is typically used in direct compression formulations. It is insoluble in water, but its surface is alkaline and it is therefore incompatible with drugs sensitive to alkaline pFI. Additionally, it may interfere with the absorption of tetracyclines [7]. 

An IPC-ESI-MS/MS method allowed the simultaneous determination of neomycin and bacitracin in human and rabbit sera [79] and the analysis of aminoglycoside antibiotics in human plasma [80]. IPC was recently validated for the estimation of bulk and formulated gatifloxacin [81]. The IPC determination of norfloxacin in diverse matrices worked as a stability indicating method [82], A CI2 stationary phase with embedded polar group successfully achieved IPC baseline tetracycline separation simply by using a phosphate as the IPR [83], A practical IPC method for the quality control of fosfomycin calcium and its related substances was recently suggested [84],... 

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