Determination of water content in tobramycin crystals by Karl Fischer volumetric method

Because the solubility of tobramycin solid particles in commonly used titration solvents is not large, it is difficult to quickly and accurately determine the water content using the conventional Karl Fischer volumetric method. This article discusses two new methods for the accurate determination of the water content of tobramycin. These two methods are also applicable to other aminoglycoside substances with little solubility in the Kaposi working solvent.

Tobramycin is a second-generation aminoglycoside antibiotic with broad-spectrum antibacterial activity obtained from the fermentation of Streptomyces nigroides [1] (Figure 1). It can inhibit Gram-negative bacteria at low concentration and has a strong inhibitory effect on Pseudomonas aeruginosa. It is 2 to 8 times stronger than other aminoglycoside antibiotics and is widely used in clinical practice. Tobramycin generally exists in the form of powder crystals, which has good fluidity and stability, and is conducive to storage, transportation and further processing. Tobramycin has strong hygroscopicity [2], and it is easy to absorb moisture directly and cause agglomeration and agglomeration. Therefore, in the production and storage of tobramycin, a fast and accurate water is required The content detection method to monitor the water content of tobramycin products, so far, the detection method of tobramycin water content is rarely reported. The Karl Fischer titration method, referred to as the Karl Fischer titration method, is a new method for determining the water content of samples based on the Karl Fischer reaction [3]. The determination result of the Karl Fischer titration method is accurate and reliable, with good repeatability and short titration time. It has been listed as the standard method for the rapid determination of moisture in many substances.

In the Karl Fischer titration process, the water in the sample needs to be in direct contact with the solvent to be detected [4], which requires that the sample must be completely dissolved in the titration solvent, so that the water in the sample is fully released. In the Karl Fischer reaction, methanol is generally used as the working solvent, but tobramycin is only slightly soluble in methanol, so improving the solubility of tobramycin in the working medium becomes the determination of the water content of tobramycin by the Karl Fischer titration method. premise. In this paper, two methods of sample processing for carbachian water analysis are established, and the chemical structure of tobramycin is accurately determined based on the chemical structure of tobramycin in Figure 1. At the same time, the analysis results of the two methods are compared accordingly.

1 Experimental materials and methods

1.1 Instruments and reagents

Karl Fischer titrator (DL18, Mettler, Switzerland)

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