(M1030-09-53) Development of Rapid LC-MS-MS Method for Therapeutic Monitoring of Plazomicin in Human Plasma

Purpose: Plazomicin is a next-generation broad-spectrum Aminoglycoside antibiotic approved in the year 2020. Like other aminoglycosides, Plazomicin is UV-transparent making its bioanalysis extremely difficult by UV-HPLC. The present study aims to develop a rapid LC-MS-MS method for the bioanalysis and therapeutic monitoring of Plazomicin in human plasma.

Methods: A validated LC-MS-MS method was developed using Agilent®-LC tendem AbSciex-API 4000 triple quad mass spectrometer for the determination of Plazomicin in human plasma. The analysis was performed using the electrospray ionization technique. Plazomicin was extracted from the plasma using the Trichloroacetic acid precipitation technique. Linearity, Accuracy, Precision and Selectivity of the method was validated.

Results: As shown in Table 1, the developed method has excellent extraction efficiency. The developed method was found to be linear within 1.25 µg/mL to 15 µg/mL concentration range of Plazomicin (Figure 1). Intra-day and inter-day variability was less than 2%. The method is selective as no peak was found in the blank and plasma containing Valinomycin. Since it does not involve the use of laborious solid phase extraction, the total time for sample preparation is short. The total run time is 5 minutes which is well accepted for therapeutic monitoring.

Conclusion: A fast and reliable bioanalytical method is highly desirable for the therapeutic monitoring of Plazomicin. Plazomicin and other aminoglycosides have extremely good water solubility. However, their solubility in an organic solvent is very poor which makes it difficult to employ commonly used protein precipitation techniques by organic solvents. Solid phase extraction can be used for bioanalysis, but it is a time-consuming process. The present study presents the development of an accurate, validated method for Plazomicin determination in human plasma using the LC-MS-MS technique for therapeutic monitoring.

Extraction efficiency in Plasma samples



Linearity of LC-MS-MS method for determination of Plazomicin within conc. Range of 1.25 ug/mL to 15 ug/mL.



LC-MS-MS chromatogram of Plazomicin