Determination of dimenhydrinate in human plasma by liquid chromatography-electrospray tandem mass spectrometry: application to a relative bioavailability study.
Here we present a sensitive and specific liquid chromatography-tandem mass spectrometric method for the quantification of dimenhydrinate (I) in human plasma. Sample preparation is conducted using citalopram (II) addition as an internal standard (IS), liquid-liquid extraction with basified plasma using a mixture hexane/acetate (1:1, v/v) as the extracting solvent, and the final extract reconstituted in the mobile phase. I and II (IS) were injected in a C8 column with the mobile phase composed of methanol:isopropanol:water:formic acid (78.00:19.92:2.00:0.08, v/v/v/v) and monitored using a positive electrospray source with tandem mass spectrometry analyses. The selected reaction monitoring (SRM) was set using precursor ion and product ion combinations of m/z 256.0>167.0 and m/z 325.0>109.0 for I and II, respectively. The limit of quantification (LOQ) was 0.4 ng/mL, the dynamic range being 0.4-200 ng/mL. Validation results on linearity, specificity, accuracy, precision and stability, as well as on application to the analysis of plasma samples taken up to 24 h after oral administration of 100 mg of dimenhydrinate in healthy volunteers demonstrated its applicability to bioavailability studies.
Tavares
V
V
Clinical Pharmacology and Gastroenterology Unit, Sao Francisco University Medical School, Av. Sao Francisco de Assis 218, 12916-900 Braganca Paulista, SP, Brazil.
Macedo
C C
CC
Montanhez
L
L
Barros
F A P
FA
Meurer
E C
EC
Campos
D R
DR
Coelho
E C
EC
Calaffati
S A
SA
Pedrazzoli
J
J
D001682:Biological Availability; D002853:Chromatography, Liquid / Q000379:methods*; D004111:Dimenhydrinate / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D006634:Histamine H1 Antagonists / Q000097:blood / Q000737:chemistry / Q000493:pharmacokinetics; D006801:Humans; D015394:Molecular Structure; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D006634:Histamine H1 Antagonists; D004111:Dimenhydrinate