Synchronous LC-MS/MS determination of pantoprazole and amitriptyline in rabbit plasma: application to comparative in vivo pharmacokinetic study of novel formulated effervescent granules with its marketed tablet dosage form

Heliyon

Hussein M. EL Messiry¹  Ehab F. El Kady²  Asmaa A. El Zaher²  Ola M. El Houssini³  Hind E. El Ghwas⁴ 

[1] Corresponding author.;Pharmaceutical Chemistry Department, Faculty of Pharmacy, Cairo University, Kasr El-Aini St., Cairo 11562, Egypt;Pharmaceutical Chemistry Department, National Organizations for Drug Control and Research (NODCAR), 51 Wezerat El- Zeraa Street, Agouza, P.O. Box 12553 Giza, 35521, Egypt;Pharmaceutics Department, National Organizations for Drug Control and Research (NODCAR), 51 Wezerat El- Zeraa Street, Agouza, P.O. Box 12553 Giza, 35521, Egypt;

关键词: LC-MS/MS;    Pantoprazole;    Amitriptyline;    Effervescent granules;    Bioanalysis;    Pharmacokinetics;   

DOI  :  

来源: DOAJ

【 摘 要 】

In the present study the bioavailability and pharmacokinetics properties of pantoprazole (proton pump inhibitor)/amitriptyline (tricyclic antidepressant) in novel formulated effervescent granules was estimated in rabbit plasma using a validated, selective and rapid LC-MS/MS method. Separation and detection of pantoprazole, amitriptyline and internal standards namely omeprazole and dothiepin, respectively, were achieved at ambient column temperature on C18. Acetonitrile: 4mM ammonium acetate solution (comprising 0.05 % formic acid) (40:60, v/v) was used as mobile phase and the flow rate of 0.6 mLmin-1 was applied. Liquid-liquid extraction technique with diethyl ether: dichloromethane (70:30, v/v) was used to extract the cited drugs from rabbit plasma. Multiple reactions monitoring (MRM) in the positive ionization mode was carried out for quantification. The method was validated over linear concentration range of 0.01-4μgmL−1 and 0.001–0.1 μgmL−1 for Pan and Ami respectively, with regression coefficient (r2) ≥ 0.9961. The intra- and inter-run precisions (%CV) were ≤4.03. The extraction recoveries were in the range of 95.92%–100.24 %. Pan and Ami were stable during three freeze-thaw cycle and post-preparative stability. The work also aimed to formulate immediate release novel effervescent granules by melt granulation technique. Nine formulae were assessed by validated dissolution test for their micrometric properties and dissolution profile. Experimental design was applied to select formula that fulfilled the desired criteria of optimum release of pantoprazole and amitriptyline with optimum micrometric properties for the study. A single period randomized open-label parallel design was applied on Chancellor's rabbit. The selected formula showed superior pharmacokinetic parameters for pantoprazole and amitriptyline than that of marketed products.

【 授权许可】

Unknown