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Development of a simple and rapid HPLC-MS/MS method for quantification of streptomycin in mice and its application to
Zhijun Wang1,2, Chen Xie3, Steven Yeung2
1Department of Pharmaceutical Sciences, Marshall B. Ketchum University, Fullerton, CA, USA.
Abstract:
Streptomycin was the first discovered aminoglycoside antibiotic. It has been widely applied in veterinary medicine for the prevention and treatment of bacterial infection. However, the current detection methods are not satisfactory in terms of sensitivity and sample process, which makes them unsuitable for a pharmacokinetic study. A high-performance liquid chromatography-mass spectrometric method employing positive electrospray ionization was developed and validated for the determination of streptomycin concentration in mice plasma. A simple protein precipitation method was utilized to extract streptomycin as well as the internal standard (kanamycin) from mouse plasma. This assay method was validated in terms of specificity, sensitivity, precision, accuracy and recovery. This method was applied to a pharmacokinetic study in mice following intramuscular administration of 200 mg/kg streptomycin. The lower limit of quantification of the developed assay method for streptomycin was 10 ng/mL. The intra-day and inter-day precision was evaluated with the coefficient of variations <14.3%, whereas the mean accuracy ranged from 87.0 to 105.0%. The samples were stable under the experimental conditions. The present method provides a robust, fast and sensitive analytical approach for the quantification of streptomycin in mouse plasma and has been successfully applied to a pharmacokinetic study in mice.
Insights
A new, sensitive method accurately measures streptomycin in mouse plasma for pharmacokinetic studies. This high-performance liquid chromatography-mass spectrometry approach improves upon existing detection limitations.
Area of Science:
- Pharmacology and Toxicology
- Analytical Chemistry
- Veterinary Medicine
Background:
- Streptomycin, an early aminoglycoside antibiotic, is vital in veterinary medicine for bacterial infections.
- Existing detection methods lack the sensitivity and efficiency required for pharmacokinetic analysis.
- This limitation hinders comprehensive studies on streptomycin's behavior in animal models.
Purpose of the Study:
- To develop and validate a sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS) method for quantifying streptomycin in mouse plasma.
- To apply the validated method in a pharmacokinetic study of streptomycin in mice.
Main Methods:
- Development of an HPLC-MS method with positive electrospray ionization.
- Utilization of protein precipitation for sample extraction of streptomycin and kanamycin (internal standard).
- Validation of the assay for specificity, sensitivity, precision, accuracy, and recovery.
Main Results:
- The developed method achieved a lower limit of quantification of 10 ng/mL for streptomycin.
- Assay validation demonstrated good precision (CV <14.3%) and accuracy (87.0-105.0%).
- The method proved robust, fast, and sensitive, successfully applied to mouse plasma samples.
Conclusions:
- A validated HPLC-MS method offers a reliable analytical tool for streptomycin quantification in mouse plasma.
- This method overcomes limitations of previous techniques, enabling accurate pharmacokinetic studies.
- The findings support the use of this method for evaluating streptomycin's drug disposition in vivo.
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