Effect of Buffer Solution and Temperature on the Stability of Penicillin G

Abstract

The effect of medium, molar ratio of buffer to penicillin G sodium, pH, and temperature on the stability of penicillin G sodium was investigated. The stability of penicillin G sodium in various media is in the order of: citrate buffer > acetate buffer > phosphate buffer > sodium bicarbonate > 0.9 % NaCl and 5 % glucose. In the case of the citrate buffer, to maintain stability for a long time, the molar ratio should be higher than 0.75. The degradation kinetics of penicillin in citrate buffer was determined over a pH range of 4.0 to 10.0 and temperatures from (5 to 50) °C. By plotting the data of log k versus pH at constant temperature, V-shaped curves were obtained with a minimum around pH 7.0. The plots of ln k versus 1/T at constant pH are linear, and the lines at all pH values are almost parallel to each other. By fitting to the Arrhenius equation, the activated energy obtained is 83.5 kJ • mol -1 • K -1 . The best condition to maintain reasonable stability of penicillin G sodium is using the citrate buffer solution with a molar ratio of buffer to penicillin g 0.75, pH ≈ 7.0, temperature e 25 °C.

Simultaneous determination of seven β-lactam antibiotics in human plasma for therapeutic drug monitoring and pharmacokinetic studies

“…While further study on the effect of methanol on individual -lactams (possibly differential effect) is warranted, we avoided it both as a mobile phase and as a precipitant. Among other precipitants tested, 10% TCA led to noticeable degradation possibly because, in the presence of an acid in high concentration, degradation of -lactams is very likely due to instability of the four member -lactam ring [44,75]. -lactams are also unstable when zinc sulphate is used as a precipitant despite the latter being very efficient protein precipitant [55].…”

A preparative method for the purification of isopenicillin N from genetically blocked Acremonium chrysogenum strain TD189: studies on the degradation kinetics and storage conditions

“…We avoided deproteinization of culture broths by acidification, because IPN, similar to other blactams, is sensitive to strong pH. 11,12 IPN is adsorbed by active charcoal, 13 but we found that this adsorption was so weak that a high volume of charcoal was required to avoid saturation. As charcoal does not produce a selective retention of significant amounts of IPN, we used charcoal to decolorize the broth (originally brown-orange colored), obtaining a clear and slightly yellow eluate.…”

“…11,12 IPN has a similar behavior to this compound, being stable at neutral pH. However, unlike benzylpenicillin, whose stability decreases at similar levels at acidic or basic pH levels, 12 IPN is slightly more stable at acidic rather than basic pH levels. Finally, both compounds are stable at lower temperatures.…”

The use of liquid chromatography-tandem mass spectrometry for therapeutic drug monitoring of antibiotics in cancer patients

“…: methanol or acetonitrile [64,72,74]. Even though the use of acidic solutions such as trichloroacetic acid (TCA) has been used successfully, care must be taken due to the instability of the four member β-lactam ring and its consequent degradation in high acid concentration [73,75]. It seems, on the other hand, that the concentration of acid that increases the degradation is antibiotic dependent.…”