Detection of dexmedetomidine in human breast milk using liquid chromatography-tandem mass spectrometry: Application to a study of drug safety in breastfeeding after Cesarean section

J Chromatogr B Analyt Technol Biomed Life Sci. 2017 Jan 1:1040:208-213. doi: 10.1016/j.jchromb.2016.11.015. Epub 2016 Nov 10.

Abstract

Several analytical methods for dexmedetomidine (DEX) in human plasma have been published, but quantification of DEX in human breast milk has not been described. In this article, we describe a high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method suitable for quantification of DEX in human breast milk. DEX and an internal standard were extracted in a single liquid-liquid extraction step with diethyl ether from 200μL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3mL/min using a mobile phase of 5mM ammonium formate:0.1% formic acid in acetonitrile (60:40, v/v). Detection was performed using an API4000 mass spectrometer with positive electrospray ionization. The method was validated in the concentration range of 10pg/mL (lower limit of quantification) to 2000pg/mL. The intra- and inter-day accuracy were within ±5.8% and precision was <6.31% based on the coefficient of variation. The recoveries of DEX in human breast milk were 82.4-87.9%. Recovery and matrix effects were consistent and reproducible for human breast milk. The method is robust and was successfully used in a study of drug safety in breastfeeding in patients after administration of DEX.

Keywords: Breastfeeding; Dexmedetomidine; HPLC–MS/MS; Human breast milk; Relative infant dose.

Publication types

  • Validation Study

MeSH terms

  • Adult
  • Breast Feeding
  • Chromatography, High Pressure Liquid / methods*
  • Dexmedetomidine / analysis*
  • Dexmedetomidine / therapeutic use
  • Female
  • Humans
  • Hypnotics and Sedatives / analysis*
  • Hypnotics and Sedatives / therapeutic use
  • Limit of Detection
  • Liquid-Liquid Extraction / methods
  • Milk, Human / chemistry*
  • Reproducibility of Results
  • Spectrometry, Mass, Electrospray Ionization / methods
  • Tandem Mass Spectrometry / methods*
  • Young Adult

Substances

  • Hypnotics and Sedatives
  • Dexmedetomidine