Multiplex Assay of Second-Line Anti-Tuberculosis Drugs in Dried Blood Spots Using Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry
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초록
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.
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.
참고문헌 (16)
- Sotgiu G, "Therapeutic drug monitoring: how to improve drug dosage and patient safety in tuberculosis treatment", Int J Infect Dis, 32, pp.101~104 (2015)
- Park JS, "Serum levels of antituberculosis drugs and their effect on tuberculosis treatment outcome", Antimicrob Agents Chemother, 60, pp.92~98 (2015)
- Srivastava S, "Multidrug-resistant tuberculosis not due to noncompliance but to between-patient pharmacokinetic variability", J Infect Dis, 204, pp.1951~1959 (2011)
- Pasipanodya JG, "Meta-analysis of clinical studies supports the pharmacokinetic variability hypothesis for acquired drug resistance and failure of antituberculosis therapy", Clin Infect Dis, 55, pp.169~177 (2012)
- Han M, "Method for simultaneous analysis of nine second-line anti-tuberculosis drugs using UPLC-MS", MS, 2013, pp.68, 2066~2073
- Vu DH, "Dried blood spots: a new tool for tuberculosis treatment optimization", Curr Pharm Des, 17, pp.2931~2939 (2011)
- Vu DH, "Determination of moxifloxacin in dried blood spots using LC-MS", MS and the impact of the hematocrit and blood volume, 2011, pp.879, 1063~1070
- Vu DH, "Dried blood spot analysis for therapeutic drug monitoring of li nezolid in patients with multidrug-resistant tuberculosis", Antimicrob Agents Chemother, 56, pp.5758~5763 (2012)
- Vu DH, "Simultaneous determination of rifampicin, clarithromycin and their metabolites in dried blood spots using LC-MS", MS, 2014, pp.121, 9~17
- 김보람, "Dried Blood Spot Testing for Seven Steroids Using Liquid Chromatography-Tandem Mass Spectrometry With Reference Interval Determination in the Korean Population", Annals of Laboratory Medicine, 35(6), pp.578~585 (2015), 대한진단검사의학회
- Elisa Legnini, "Analysis of Acid Sphingomyelinase Activity in Dried Blood Spots Using Tandem Mass Spectrometry", Annals of Laboratory Medicine, 32(5), pp.319~323 (2012), 대한진단검사의학회
- Annesley TM, "Ion suppression in mass spectrometry", Clin Chem, 49, pp.1041~1044 (2003)
- Clinical Laboratory Standards Institute, "Evaluation of the linearity of quantitative measurement procedures: a statistical approach; approved guideline. CLSI Document EP6-A", Clinical Laboratory Standards Institute, ~ (2003)
- Park SI, "Pharmacokinetics of second-line antituberculosis drugs after multiple administrations in healthy volunteers", Antimicrob Agents Chemother, 59, pp.4429~4435 (2015)
- Mukaka MM, "Statistics corner: A guide to appropriate use of correlation coefficient in medical research", Malawi Med J, 24, pp.69~71 (2012)
- Capiau S, "Prediction of the hematocrit of dried blood spots via potassium measurement on a routine clinical chemistry analyzer", Anal Chem, 85, pp.404~410 (2013)