title: Liquid chromatography-tandem mass spectrometric determination of propofol in rat serum and hair at attogram level after derivatization with 3-bromomethyl-propyphenazone.
abstract: A sensitive, selective and precise liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for determination of propofol (PRO) in rat serum and hair has been developed. 3-Bromomethyl-propyphenazone was used as derivatization reagent forming propofol-methyl-propyphenazone compound. The derivatization reaction was optimized and validated for maximum MS sensitivity. The MS instrumental sensitivity reached to 10 attogram. The serum samples were extracted by using Chromabond C8columns, while hair samples extracted with methanol. The tendency of volatility of PRO was minimized by adding triethylamine to the extract before the use of nitrogen gas for evaporation of solvent. The limit of quantitation (LLOQ) was 0.01pg/mL and the assay was linear to 10000pg/mL. The intra-and inter-day precision (RSD%) ranged from 0.33 to 3.44% while the accuracy (Er%, relative error) were -6.4 to 1.1%. The ionization suppression, due to reagent, was minimized by reacting the excess reagent with methanol, and eluting to waste before MS ionization source (2-4.5min). The method was successfully applied for detection and determination of PRO in rat serum and hair after 7-28days from administration of only one dose of propofol (10mg/kg).
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, P.O. Box 80260, Saudi Arabia. Electronic address: akhedr@kau.edu.sa.
authors.forename: Alaa
authors.initials: A
authors.lastname: Khedr
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, P.O. Box 80260, Saudi Arabia; Faculty of Pharmacy, Department of Analytical Chemistry, Zagazig University, Egypt.
authors.forename: Soad S Abd
authors.initials: SSA
authors.lastname: El-Hay
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmacy, King Abdulaziz University, Jeddah 21589, P.O. Box 80260, Saudi Arabia.
authors.forename: Ahmed K
authors.initials: AK
authors.lastname: Kammoun
mesh_terms: D000818:Animals; D000983:Antipyrine / Q000031:analogs & derivatives* / Q000737:chemistry; D002853:Chromatography, Liquid / Q000379:methods; D006197:Hair / Q000737:chemistry*; D006993:Hypnotics and Sedatives / Q000097:blood / Q000737:chemistry; D008297:Male; D015742:Propofol / Q000097:blood* / Q000737:chemistry*; D051381:Rats; D017208:Rats, Wistar; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: C112340:3-bromomethylpropyphenazone; D006993:Hypnotics and Sedatives; D000983:Antipyrine; D015742:Propofol
keywords: 3-Bromomethyl-propyphenazone; Attogram; Derivatization; Hair; Liquid chromatography tandem mass spectrometry; Propofol; Serum