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Determination of moxifloxacin in dried blood spots using LC–MS/MS and the impact of the hematocrit and blood volume
- Source :
- Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 879(15-16), 1063-1070. ELSEVIER SCIENCE BV
- Publication Year :
- 2011
- Publisher :
- Elsevier BV, 2011.
-
Abstract
- Moxifloxacin (MFX) is a potential oral agent use in the treatment of multidrug-resistance tuberculosis (MDR-TB). Due to variability in pharmacokinetics and in vitro susceptibility of causative bacteria, therapeutic drug monitoring (TDM) of MFX is recommended. Conventional plasma sampling for TDM is facing logistical challenges, especially in limited resource areas, and dried blood spots (DBS) sampling may offer a chance to overcome this problem. The objective of this study was to develop a LC-MS/MS method for determination of MFX in dried blood spots (DBS) that is applicable for TDM. The influence of paper type, the hematocrit (Hct) and the blood volume per spot (V(b)) on the estimated blood volume in a disc (V(est)) was investigated. The extracts of 8mm diameter discs punched out from DBS were analyzed using liquid chromatography tandem mass spectrometry (LC-MS/MS) with cyanoimipramin as internal standard. The method was validated with respect to selectivity, linearity, accuracy, precision, sensitivity, recovery and stability. The effect of Hct and V(b) on LC-MS/MS analytical result was also investigated. The relationship between MFX concentrations in venous and finger prick DBS and those in plasma was clinically explored. V(est) was highly influenced by Hct while the effect of V(b) appeared to be different among paper types. Calibration curves were linear in the range of 0.05-6.00 mg/L with inter-day and intra-day precisions and biases of less than 11.1%. The recovery was 84.5, 85.1 and 92.6% in response to blood concentration of 0.15, 2.50 and 5.00 mg/L, respectively. A matrix effect of less than 11.9% was observed. MFX in DBS was stable for at least 4 weeks at room condition (temperature of 25°C and humidity of 50%). A large range of Hct value produced a significant analytical bias and it can be corrected with resulting DBS size. A good correlation between DBS and plasma concentrations was observed and comparable results between venous DBS and finger prick DBS was attained. This fully validated method is suitable for determination of MFX in dried blood spot and applicable for TDM.
- Subjects :
- Moxifloxacin
Clinical Biochemistry
Antitubercular Agents
Dried blood spot
Blood volume
Hematocrit
Sensitivity and Specificity
Biochemistry
High-performance liquid chromatography
Analytical Chemistry
Drug Stability
CEREBROSPINAL-FLUID
Pharmacokinetics
Tandem Mass Spectrometry
Liquid chromatography–mass spectrometry
medicine
Humans
Tuberculosis
LC-MS/MS
TANDEM MASS-SPECTROMETRY
MULTIDRUG-RESISTANT TUBERCULOSIS
Antibacterial agent
Aza Compounds
Blood Specimen Collection
Blood Volume
Chromatography
PLASMA
medicine.diagnostic_test
Chemistry
Reproducibility of Results
Cell Biology
General Medicine
QUANTITATIVE-ANALYSIS
Therapeutic drug monitoring
Linear Models
Quinolines
PHASE-II
MYCOBACTERIUM-TUBERCULOSIS
Drug Monitoring
FILTER-PAPER
Chromatography, Liquid
Fluoroquinolones
Subjects
Details
- ISSN :
- 15700232
- Volume :
- 879
- Database :
- OpenAIRE
- Journal :
- Journal of Chromatography B
- Accession number :
- edsair.doi.dedup.....e58429a43c3da8879f10d0f0eda556d3