Multiplex Assay of Second-Line Anti-Tuberculosis Drugs in Dried Blood Spots Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry.
10.3343/alm.2016.36.5.489
- Author:
Kyunghoon LEE
1
;
Sun Hee JUN
;
Minje HAN
;
Sang Hoon SONG
;
Jong Sun PARK
;
Jae Ho LEE
;
Kyoung Un PARK
;
Junghan SONG
Author Information
1. Department of Laboratory Medicine, Seoul National University College of Medicine, Seoul, Korea. songjhcp@snu.ac.kr
- Publication Type:Brief Communication
- Keywords:
Anti-tuberculosis drug;
Tandem mass spectrometry;
Dried blood spot;
Multiplex analysis;
Therapeutic drug monitoring
- MeSH:
Antitubercular Agents/*blood;
Chromatography, High Pressure Liquid;
*Dried Blood Spot Testing;
Humans;
Limit of Detection;
Reproducibility of Results;
*Tandem Mass Spectrometry
- From:Annals of Laboratory Medicine
2016;36(5):489-493
- CountryRepublic of Korea
- Language:English
-
Abstract:
As dried blood spots (DBSs) have various advantages over conventional venous blood sampling, some assays for detection of one or two anti-tuberculosis (TB) drugs in DBSs have been developed. However, there are no assays currently available for the simultaneous measurement of three or more anti-TB drugs in DBSs. In this study, we developed and evaluated a multiplex method for detecting nine anti-TB drugs including streptomycin, kanamycin, clarithromycin, cycloserine, moxifloxacin, levofloxacin, para-aminosalicylic acid, prothionamide, and linezolid in DBSs by using ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). Seventy-nine patient samples of DBS were analyzed on the UPLC-MS/MS system. All drug concentrations were determined within 4 min, and assay performance was evaluated. All drugs were clearly separated without ion suppression. Within-run and between-run precisions were 1.7-13.0% and 5.7-17.0%, respectively, at concentrations representing low and high levels for the nine drugs. Lower limits of detection and quantification were 0.06-0.6 and 0.5-5.0 µg/mL, respectively. Linearity was acceptable at five level concentrations for each drug. Correlations between drug concentrations in plasma and DBSs by using Passing-Bablock regression and Pearson's rho (ρ, 0.798-0.989) were acceptable. In conclusion, we developed a multiplex assay to measure nine second-line anti-TB drugs in DBSs successfully. This assay provided convenient and rapid drug quantification and could have applications in drug monitoring during treatment.
