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LC-MS-MS Method for the Analysis of New Non-Imidazole Histamine H₃ Receptor Antagonist 1-[3-(4-tert-Butylphenoxy)propyl]piperidine in Rat Serum--Application to Pharmacokinetic Studies

Szafarz, Malgorzata, Szymura-Oleksiak, Joanna, Lazewska, Dorota, Kiec-Kononowicz, Katarzyna
Chromatographia 2011 v.73 no.9-10 pp. 913-919
acetonitrile, antagonists, blood serum, detection limit, formic acid, histamine, intravenous injection, ionization, liquid chromatography, pharmacokinetics, piperidines, rats, spectrometers, tandem mass spectrometry, Ireland, Ontario
A sensitive and specific liquid chromatography electrospray ionisation-tandem mass spectrometry method for determination of new non-imidazole histamine H₃ receptor antagonist 1-[3-(4-tert-butylphenoxy)propyl]piperidine (DL76) in rat serum has been developed and validated. Chromatography was performed on a XBridge™ C18 analytical column (2.1 × 30 mm, 3.5 µm, Waters, Ireland) with gradient elution using a mobile phase containing acetonitrile and water with an addition of 0.1% of formic acid. Detection was achieved by an Applied Biosystems MDS Sciex (Concord, Ontario, Canada) API 2000 triple quadrupole mass spectrometer. Electrospray ionization (ESI) was used for ion production. The limit of detection in the SRM mode was found to be 0.5 ng mL⁻¹. The limit of quantification was 1 ng mL⁻¹. The precision and accuracy for both intra- and inter-day determination of DL76 ranged from 1.65 to 15.09% and from 88.74 to 113.43%. The results of this analytical method validation allow to carry out pharmacokinetic studies in rats. The method was used for the pilot study of the pharmacokinetic behavior of DL76 in rats after intravenous administration.