Measurement of tigecycline in dried blood spots by LC–MS/MS and comparison tigecycline concentrations between whole blood and plasma

Abstract

Rationale An LC–MS/MS method was established to measure tigecycline in dried blood spots (DBSs). Methods The DBS specimens obtained by applying 30 μl of blood to filter paper were extracted with hydrogen oxide and subsequently precipitated protein with perchloric acid, then the extract was directly analyzed by liquid chromatography tandem mass spectrometry. A Hypersil GOLD aQ column was utilized for separating the analytes, and detection was carried out in positive and selective reaction monitoring modes. The precursors to product ion transitions m/z 586.3 → 513.1 and m/z 586.3 → 569.2 were monitored for tigecycline, and m/z 473.2 → 456.0 and m/z 473.2 → 367.0 for 9‐amino minocycline as internal standard. Results The validation parameters of specificity and selectivity, linearity (0.02–5 μg ml−1), sensitivity (limit of quantification 0.02 μg ml−1), intra‐ and interday precision (within 15%) and relative error (within ±15%) were acceptable. The recoveries were from 84.65% to 90.49% and from 85.41% to 95.72% for tigecycline and internal standard, respectively, and the matrix effect was not evident to influence accuracy. The impact of hematocrit on measurement of the analyte was negligible, and after preserving at ambient temperature for 24 h and at 4°C for 1 month it remained steady. Conclusions The advantages of nonintrusive blood collection and micro‐volume sample requirements make DBS a potent surrogate to conventional venepuncture for sampling.