title: Selective microemulsion liquid chromatography analysis of dopamine receptor antagonist LE300 and its N-methyl metabolite in mouse sera by using a monolithic silica column.
abstract: A highly selective, sensitive, and rapid microemulsion liquid chromatography (MELC) method was developed and validated for the simultaneous determination of a novel type of dopamine receptor antagonist LE300 and its N-methyl metabolite in mouse sera. LE300, its N-methyl metabolite, and pindolol (an internal standard) were detected using excitation and emission wavelengths of 275 and 340 nm, respectively. HPLC analysis by using a monolithic column was performed by directly injecting the sample after appropriate dilution with the microemulsion mobile phase. The chromatographic behaviour of these compounds was studied to demonstrate their chromatographic efficiency, retention, and peak symmetry. The MELC method was validated for its specificity, linearity, accuracy, precision, robustness and stability. An experimental design was used during validation to evaluate method robustness. The calibration curves in serum showed excellent linearity (r=0.997) over concentrations ranging from 10 to 400 ngmL(-1) for LE300 and 15 to 500 ngmL(-1) for its N-methyl metabolite. The mean relative standard deviation (RSD) of the results of inter- and intra-day precision and accuracy of LE300 and its N-methyl metabolite were ≤5%. The overall recoveries of LE300 and its N-methyl metabolite from mouse sera were in the range 97.9-101.5% with %RSD ranging from 0.98% to 3.63%, which were in line with ICH guidelines. The assay was successfully applied in a pharmacokinetic study.
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
authors: Abdulrhman A
authors: AA
authors: Al-Majed
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia. Electronic address: mhefnawy2003@yahoo.com.
authors: Mohamed M
authors: MM
authors: Hefnawy
authors: Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
authors: Mostafa S
authors: MS
authors: Mohammed
authors: Department of Pharmacology, College of Pharmacy, King Saud University, P. O. Box 2457, Riyadh 11451, Saudi Arabia.
authors: Sabry M
authors: SM
authors: Attia
authors: Institut fur Pharmazie, Lehrstuhl fur Pharmazeutische/Medizinische Chemie, Friedrich Schiller Universitat Jena, Jena, Germany.
authors: Jochen
authors: J
authors: Lehmann
mesh_terms: D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000295:instrumentation / Q000379:methods*; D018492:Dopamine Antagonists / Q000097:blood* / Q000493:pharmacokinetics; D007211:Indoles / Q000097:blood* / Q000493:pharmacokinetics; D008297:Male; D051379:Mice; D012822:Silicon Dioxide / Q000737:chemistry
chemical_list: C409874:7-methyl-6,7,8,9,14,15-hexahydro-5H-benz(d)indolo(2,3-g)azecine; D018492:Dopamine Antagonists; D007211:Indoles; D012822:Silicon Dioxide
keywords: LE300; Microemulsion liquid chromatography; Monolithic column; Serum Pharmacokinetics