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

Rika Nakanishi, Manabu Yoshimura, Manabu Suno, Kento Yamamoto, Haruka Ito, Yohei Uchimine, Takashi Toriumi, Atsushi Kurosawa, Ami Sugawara, Takayuki Kunisawa

Research output: Contribution to journalArticle

9 Citations (Scopus)

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 200 μL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3 mL/min using a mobile phase of 5 mM 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 10 pg/mL (lower limit of quantification) to 2000 pg/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.

Original languageEnglish
Pages (from-to)208-213
Number of pages6
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1040
DOIs
Publication statusPublished - Jan 1 2017

Fingerprint

Dexmedetomidine
Human Milk
Breast Feeding
Cesarean Section
Mass spectrometry
Mass Spectrometry
formic acid
Safety
Liquids
Pharmaceutical Preparations
Plasma (human)
Recovery
Electrospray ionization
Mass spectrometers
Ether
Gels
Flow rate
High Pressure Liquid Chromatography

Keywords

  • Breastfeeding
  • DEX
  • dexmedetomidine
  • Dexmedetomidine
  • HPLC–MS/MS
  • Human breast milk
  • internal standard
  • IS
  • liquid–liquid extraction
  • LLE
  • M/P
  • milk to plasma concentration ratio
  • MRM
  • multiple reaction monitoring
  • relative infant dose
  • Relative infant dose
  • RID
  • solid phase extraction
  • SPE

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

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. / Nakanishi, Rika; Yoshimura, Manabu; Suno, Manabu; Yamamoto, Kento; Ito, Haruka; Uchimine, Yohei; Toriumi, Takashi; Kurosawa, Atsushi; Sugawara, Ami; Kunisawa, Takayuki.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1040, 01.01.2017, p. 208-213.

Research output: Contribution to journalArticle

Nakanishi, Rika ; Yoshimura, Manabu ; Suno, Manabu ; Yamamoto, Kento ; Ito, Haruka ; Uchimine, Yohei ; Toriumi, Takashi ; Kurosawa, Atsushi ; Sugawara, Ami ; Kunisawa, Takayuki. / 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. In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2017 ; Vol. 1040. pp. 208-213.
@article{e46cea549f744f27ac9fc97e1c6cdabe,
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 200 μL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3 mL/min using a mobile phase of 5 mM 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 10 pg/mL (lower limit of quantification) to 2000 pg/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, DEX, dexmedetomidine, Dexmedetomidine, HPLC–MS/MS, Human breast milk, internal standard, IS, liquid–liquid extraction, LLE, M/P, milk to plasma concentration ratio, MRM, multiple reaction monitoring, relative infant dose, Relative infant dose, RID, solid phase extraction, SPE",
author = "Rika Nakanishi and Manabu Yoshimura and Manabu Suno and Kento Yamamoto and Haruka Ito and Yohei Uchimine and Takashi Toriumi and Atsushi Kurosawa and Ami Sugawara and Takayuki Kunisawa",
year = "2017",
month = "1",
day = "1",
doi = "10.1016/j.jchromb.2016.11.015",
language = "English",
volume = "1040",
pages = "208--213",
journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences",
issn = "1570-0232",
publisher = "Elsevier",

}

TY - JOUR

T1 - Detection of dexmedetomidine in human breast milk using liquid chromatography–tandem mass spectrometry

T2 - Application to a study of drug safety in breastfeeding after Cesarean section

AU - Nakanishi, Rika

AU - Yoshimura, Manabu

AU - Suno, Manabu

AU - Yamamoto, Kento

AU - Ito, Haruka

AU - Uchimine, Yohei

AU - Toriumi, Takashi

AU - Kurosawa, Atsushi

AU - Sugawara, Ami

AU - Kunisawa, Takayuki

PY - 2017/1/1

Y1 - 2017/1/1

N2 - 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 200 μL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3 mL/min using a mobile phase of 5 mM 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 10 pg/mL (lower limit of quantification) to 2000 pg/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.

AB - 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 200 μL of human breast milk. HPLC was performed on a TSK-gel ODS-100V column with isocratic elution at a flow rate of 0.3 mL/min using a mobile phase of 5 mM 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 10 pg/mL (lower limit of quantification) to 2000 pg/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.

KW - Breastfeeding

KW - DEX

KW - dexmedetomidine

KW - Dexmedetomidine

KW - HPLC–MS/MS

KW - Human breast milk

KW - internal standard

KW - IS

KW - liquid–liquid extraction

KW - LLE

KW - M/P

KW - milk to plasma concentration ratio

KW - MRM

KW - multiple reaction monitoring

KW - relative infant dose

KW - Relative infant dose

KW - RID

KW - solid phase extraction

KW - SPE

UR - http://www.scopus.com/inward/record.url?scp=85006678302&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85006678302&partnerID=8YFLogxK

U2 - 10.1016/j.jchromb.2016.11.015

DO - 10.1016/j.jchromb.2016.11.015

M3 - Article

C2 - 27856195

AN - SCOPUS:85006678302

VL - 1040

SP - 208

EP - 213

JO - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

JF - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences

SN - 1570-0232

ER -