highly sensitive LC-MS/MS method capable of simultaneously quantitating celiprolol and atenolol in human plasma for a cassette cold-microdosing study

• Published in: Journal of separation science Vol. 34; no. 13; pp. 1590 - 1598
• Main Authors: Minamide, Yoshiyuki, Osawa, Yukio, Nishida, Hiroshi, Igarashi, Harue, Kudoh, Shinobu
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag 01.07.2011; WILEY-VCH Verlag; WILEY‐VCH Verlag; Wiley; Wiley Subscription Services, Inc
• Subjects: Analysis; Antihypertensive Agents; Antihypertensive Agents - blood; Antihypertensive Agents - isolation & purification; Atenolol; Atenolol - blood; Atenolol - isolation & purification; beta-adrenergic antagonists; Biological and medical sciences; blood; Cartridges; Cassettes; cation exchange; Celiprolol; Celiprolol - blood; Celiprolol - isolation & purification; Chromatography; Chromatography, High Pressure Liquid; Chromatography, High Pressure Liquid - methods; Dispersion hardening alloys; Extraction; formic acid; General pharmacology; Human; Humans; ionization; isolation & purification; LC-MS; mass spectrometry; Medical sciences; methanol; methods; Methyl alcohol; Microdosing; Pharmacology. Drug treatments; reversed-phase chromatography; reversed-phase liquid chromatography; Sensitivity and Specificity; Separation; Solid Phase Extraction - methods; Solid-phase extraction; spectrometers; Tandem Mass Spectrometry; Tandem Mass Spectrometry - methods; β-blocker; Solid phase extraction; Biological fluid; Tandem mass spectrometry; Chemical analysis; Vasodilator agent; Celiprolol; HPLC chromatography; Electrospray; Blood; Microdosing; Chemical enrichment; Blood plasma; β1-Adrenergic receptor; Sample preparation; Antagonist; Quantitative analysis; Trace analysis; Human; Validation; Healthy subject; Coupled method; MS; Oral administration; Atenolol; Solid-phase extraction; β-blocker; Reversed phase chromatography; LC-MS; Simultaneous measurement; Antihypertensive agent; Pharmacokinetics; Cation exchanger; Beta blocking agent
• ISSN: 1615-9306; 1615-9314; 1615-9314
• DOI: 10.1002/jssc.201100089

A highly sensitive simultaneous quantitative method for a cassette cold-microdosing study on celiprolol and atenolol was developed with liquid chromatography-tandem mass spectrometry. The method utilizes a combination of solid-phase extraction (SPE) with strong cation exchange (SCX) cartridge columns and reversed-phase chromatography with an ODS analytical column. SCX-SPE cartridge columns (100 mg sorbent) were used for a selective extraction of celiprolol, atenolol and metoprolol (internal standard) from 500 μL of human plasma samples. Turbo-ion spray at positive mode was employed for the ionization of the drug compounds. Quantitation was performed on a triple quadrupole mass spectrometer by selected reaction monitoring with the transitions of m/z 380 to m/z 251 for celiprolol and m/z 267 to m/z 145 for atenolol. Separation of analytes was achieved on an ODS column (100 mm length×2.1 mm id, 3 μm) by a gradient elution with 10 mM formic acid and methanol by varying their proportion at a flow rate of 0.2 mL/min. The method was validated in the range of 1-250 pg/mL for celiprolol and 2.5-250 pg/mL for atenolol and was successfully applied to the elucidation of pharmacokinetic profiling in a cold cassette microdosing study of the β-blockers.