title: 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.
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.
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Rika
authors.initials: R
authors.lastname: Nakanishi
authors.affiliation: Department of Anesthesiology, Japan Community Healthcare Organization Tokuyama Central Hospital, 1-1 Kodacho, Shunan-City, Yamaguchi 745-8522, Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Yoshimura
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan. Electronic address: sunoma@okayama-u.ac.jp.
authors.forename: Manabu
authors.initials: M
authors.lastname: Suno
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Kento
authors.initials: K
authors.lastname: Yamamoto
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Haruka
authors.initials: H
authors.lastname: Ito
authors.affiliation: Department of Oncology Pharmaceutical Care & Sciences, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, 2-5-1, Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yohei
authors.initials: Y
authors.lastname: Uchimine
authors.affiliation: Department of Anesthesiology, Japan Community Healthcare Organization Tokuyama Central Hospital, 1-1 Kodacho, Shunan-City, Yamaguchi 745-8522, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Toriumi
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078-8510, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kurosawa
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078-8510, Japan.
authors.forename: Ami
authors.initials: A
authors.lastname: Sugawara
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Asahikawa Medical University, 2-1-1-1 Midorigaoka Higashi, Asahikawa, Hokkaido 078-8510, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kunisawa
mesh_terms: D000328:Adult; D001942:Breast Feeding; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D020927:Dexmedetomidine / Q000032:analysis* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D006993:Hypnotics and Sedatives / Q000032:analysis* / Q000627:therapeutic use; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D008895:Milk, Human / Q000737:chemistry*; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
chemical_list: D006993:Hypnotics and Sedatives; D020927:Dexmedetomidine
keywords: Breastfeeding; Dexmedetomidine; HPLC–MS/MS; Human breast milk; Relative infant dose