LB-012 - DEVELOPMENT OF LC-MS/MS METHOD FOR THE SIMULTANEOUS DETERMINATION OF ANTI-NONTUBERCULOUS MYCOBACTERIA PULMONARY DISEASE DRUGS IN HUMAN PLASMA

H. Seong¹, Y. Choi², Y. Park¹, J. Shin², D. Kim³; ¹Inje University, College of Medicine, , , ²Center for Personalized Precision Medicine of Tuberculosis, Inje University College of Medicine, , , ³Inje University, College of Medicine, Inje University, College of Medicine, Busan, South Korea.

Background: In the modern healthcare environment, where non-tuberculous lung diseases are increasingly prevalent, the efficacy of alternative and potential drugs, as well as conventional therapeutic drugs, is being studied to improve patient outcomes. To evaluate these drugs and find optimal treatment options, it is important to accurately measure drug concentrations in the blood. For this purpose, a method for the simultaneous analysis of drug concentrations using liquid chromatography-mass spectrometry (LC-MS/MS) has been developed.

Methods: To achieve the separation of anti-nontuberculous drugs including azithromycin, clofazimine, doxycycline, imipenem, linezolid, minocycline, omadacycline, sulfamethoxazole, tedizolid, tigecycline, trimethoprim, a CAP CELL PAK C18 was utilized with a gradient elution in API4000 mass spectrometer coupled with Agilent1100 series LC. The selectivity, linearity, precision, accuracy, recovery, matrix effects, and stability were evaluated as validation criteria.

Results: The calibration ranges of drugs were 0.02 to 100 ug/mL, and calibration curves were processed by weighted 1/x2 least squares linear regression. The correlation coefficients (R2) of drugs were higher than 0.98. The intra- and inter-day precision was less than 13%, and the accuracy ranged between 85.86% and 114.62%. The compounds were stable at room temperature, 4'C, -20'C for 4 hours, and 10'C in autosampler for 18 hours except for imipenem and omadacycline.

Conclusion: This robust and sensitive method of simultaneous drug quantification using LC-MS/MS has been validated and can be successfully applied to quantify drug concentrations in plasma for therapeutic drug monitoring and may contribute to the treatment of non-tuberculous mycobacterial lung disease.