title: HPLC-MS/MS method for dexmedetomidine quantification with Design of Experiments approach: application to pediatric pharmacokinetic study.
abstract: OBJECTIVE
  The purpose of this work was to develop and validate a rapid and robust LC-MS/MS method for the determination of dexmedetomidine (DEX) in plasma, suitable for analysis of a large number of samples.
  
  
  METHODS
  Systematic approach, Design of Experiments, was applied to optimize ESI source parameters and to evaluate method robustness, therefore, a rapid, stable and cost-effective assay was developed. The method was validated according to US FDA guidelines. LLOQ was determined at 5 pg/ml. The assay was linear over the examined concentration range (5-2500 pg/ml), Results: Experimental design approach was applied for optimization of ESI source parameters and evaluation of method robustness. The method was validated according to the US FDA guidelines. LLOQ was determined at 5 pg/ml. The assay was linear over the examined concentration range (R2> 0.98). The accuracies, intra- and interday precisions were less than 15%. The stability data confirmed reliable behavior of DEX under tested conditions.
  
  
  CONCLUSIONS
  Application of Design of Experiments approach allowed for fast and efficient analytical method development and validation as well as for reduced usage of chemicals necessary for regular method optimization. The proposed technique was applied to determination of DEX pharmacokinetics in pediatric patients undergoing long-term sedation in the intensive care unit.
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Oliwia
authors.initials: O
authors.lastname: Szerkus
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Wiktoria
authors.initials: W
authors.lastname: Struck-Lewicka
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Marta
authors.initials: M
authors.lastname: Kordalewska
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Bartosińska
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Renata
authors.initials: R
authors.lastname: Bujak
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Borsuk
authors.affiliation: Department of Clinical Pharmacy & Biopharmacy, Poznań University of Medical Sciences, Św. Marii Magdaleny 14, 61-861 Poznań, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Bienert
authors.affiliation: Department of Pediatric Anesthesiology & Intensive Therapy, Poznań University of Medical Sciences, Szpitalna 27/33, 60-572 Poznań, Poland.
authors.forename: Alicja
authors.initials: A
authors.lastname: Bartkowska-Śniatkowska
authors.affiliation: Department of Clinical Pharmacy & Biopharmacy, Poznań University of Medical Sciences, Św. Marii Magdaleny 14, 61-861 Poznań, Poland.
authors.forename: Justyna
authors.initials: J
authors.lastname: Warzybok
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Paweł
authors.initials: P
authors.lastname: Wiczling
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Antoni
authors.initials: A
authors.lastname: Nasal
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Roman
authors.initials: R
authors.lastname: Kaliszan
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Michał Jan
authors.initials: MJ
authors.lastname: Markuszewski
authors.affiliation: Department of Biopharmaceutics & Pharmacodynamics, Medical University of Gdańsk, Al. Gen. J. Hallera 107, 80-416 Gdańsk, Poland.
authors.forename: Danuta
authors.initials: D
authors.lastname: Siluk
mesh_terms: D002138:Calibration; D002648:Child; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003362:Cost-Benefit Analysis; D003422:Critical Care; D020927:Dexmedetomidine / Q000097:blood* / Q000493:pharmacokinetics*; D006801:Humans; D057230:Limit of Detection; D016014:Linear Models; D010372:Pediatrics; D011786:Quality Control; D015203:Reproducibility of Results; D012107:Research Design; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D020927:Dexmedetomidine
keywords: ESI; LC–MS/MS; SPE; anesthetic drug; design of experiments; detomidine; dexmedetomidine; method validation; pediatric plasma