title: Development and validation of an LC-MS/MS method for simultaneously determining doxapram and keto-doxapram in human serum.
abstract: OBJECTIVE
  Doxapram, a respiratory stimulant, is used to treat apnea. A reliable method of determining doxapram in blood is required for monitoring purposes.
  
  
  RESULTS
  Doxapram, keto-doxapram (active metabolite) and propranolol (internal standard) were extracted from human serum by protein precipitation and plate filtration. Molecular ions were generated by electrospray ionization in positive ion mode, and the ions were analyzed using a triple-quadrupole mass spectrometer. The calibration curves were linear from 20 to 5000 ng/ml. The method was validated and the selectivity, reproducibility and stability met the acceptance criteria.
  
  
  CONCLUSIONS
  An LC-MS/MS method was successfully developed for determining doxapram and keto-doxapram in human serum. The method can be used to monitor doxapram and keto-doxapram concentrations in blood.
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Suzuki
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Noboru
authors.initials: N
authors.lastname: Kamada
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Ohno
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Abe
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Takuro
authors.initials: T
authors.lastname: Endo
authors.affiliation: Central Research Laboratories, Kissei Pharmaceutical Co., Ltd, 4365-1 Kashiwabara, Hotaka, Azumino, Nagano, Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Kobayashi
mesh_terms: D002138:Calibration; D002853:Chromatography, Liquid / Q000379:methods*; D004315:Doxapram / Q000031:analogs & derivatives* / Q000097:blood*; D016903:Drug Monitoring; D004355:Drug Stability; D006801:Humans; D057230:Limit of Detection; D011433:Propranolol / Q000097:blood; D012015:Reference Standards; D015203:Reproducibility of Results; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C029505:2-ketodoxapram; D004315:Doxapram; D011433:Propranolol
keywords: LC–MS/MS; doxapram; validation