title: Is a deuterated internal standard appropriate for the reliable determination of olmesartan in human plasma?
abstract: A right choice of the internal standard is one of the most challenging tasks during bioanalytical method development. Surprisingly, among the HPLC-MS methods for the determination of a cardiovascular drug olmesartan in plasma only structural analogues or similar compounds were used as internal standards. We have tried to answer the question whether the stable isotope labelled (deuterated) internal standard, as recommended by regulatory agencies, can be used for the reliable determination of olmesartan in human plasma. An HPLC-MS method using this standard in a simplified liquid-liquid extraction procedure led to accurate and precise results in the linearity range of 5-2500ng/mL. The method is well suited for pharmacokinetic studies following a single 40mg oral dose of olmesartan medoxomil in humans. The method was fully validated according to international guidelines and successfully applied in a bioequivalence study in humans. The use of deuterated olmesartan as the internal standard afforded a reliable tool for regulatory bioanalysis that can indirectly contribute to therapy efficacy and improve the safety of patients treated with generic medicines.
authors.affiliation: Pharmaceutical Research Institute, Pharmacology Department, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Edyta
authors.initials: E
authors.lastname: Piórkowska
authors.affiliation: Pharmaceutical Research Institute, Pharmacology Department, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Jacek
authors.initials: J
authors.lastname: Musijowski
authors.affiliation: Pharmaceutical Research Institute, Pharmacology Department, 8 Rydygiera, 01-793 Warsaw, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Buś-Kwaśnik
authors.affiliation: Pharmaceutical Research Institute, Pharmacology Department, 8 Rydygiera, 01-793 Warsaw, Poland. Electronic address: p.rudzki@ifarm.eu.
authors.forename: Piotr J
authors.initials: PJ
authors.lastname: Rudzki
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000097:blood*; D000959:Antihypertensive Agents / Q000097:blood*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003903:Deuterium / Q000032:analysis; D006801:Humans; D007093:Imidazoles / Q000097:blood*; D057230:Limit of Detection; D059625:Liquid-Liquid Extraction / Q000379:methods; D008297:Male; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013777:Tetrazoles / Q000097:blood*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D000959:Antihypertensive Agents; D007093:Imidazoles; D013777:Tetrazoles; C437965:olmesartan; D003903:Deuterium
keywords: Bioanalytical method validation; Liquid chromatography/mass spectrometry; Olmesartan; Pharmacokinetics; Stable isotopically labelled internal standard