a. Department of Pharmacy; b. Department of Respiration, 1. Children′s Hospital of Hebei Province, Shijiazhuang 050031, China; 2. CSPC Ouyi Pharmaceutical Co., Ltd., Shijiazhuang 050051, China
Abstract：OBJECTIVE To establish a high performance liquid chromatography-tandem mass spectrometry method for the quantitative analysis of ertapenem in children′s plasma and evaluate the influence caused by hemolytic effect. METHODS Hypersil GOLDTM column (2.1 mm×50 mm, 3 μm) was used and the column temperature was mainteined at 40 ℃. The mobile phases was composed of water (A) and acetonitrile (B), each containing 0.1% formic acid. Gradient elution was conducted at a flow rate of 0.5 mL·min-1. The injection volume was 3 mL. Total run time was 4 min. For mass spectrometry, electrospray ionization source was chosen, and positive ion monitoring mode was used with multi-reaction monitoring (MRM) mode. The precursor-to-product ion pairs of ertapenem and meropenem (IS) for quantitation were 476.2→432.2 and 384.1→141.2, respectively. Acetonitrile containing 0.1% formic acid was used as protein precipitation. RESULTS The calibration curve was linear over a range of 0.1 to 50 μg·mL-1 (r＞0.998 0, n=6). The within-run and between-run accuracy RSDs were both less than ±15%. The within-run and between-run variable coefficients (CV) were both less than 8.5%. No significant matrix effect was observed for ertapenem and the hemolytic effect was acceptable. Ertapenem was stable for 72 h in whole blood at 5 ℃. Analytes in plasma were stable after three freeze-thaw cycles and robust for 4 h (at room temperature), 8 h (in autosampler, 5 ℃) and 30 d (-20 ℃), respectively. Incurred sample analysis was satisfactory within Ch.P guideline limits. CONCLUSION This rapid, sensitive, robust and exclusive HPLC-MS/MS assay requires small-volume of samples and simple preparation without interference by hemolytic effect, which can be applied in pharmacokinetic studies and therapeutic drug monitoring in children.
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2020, Vol. 55 
