Rapid determination of corticosterone in mouse plasma by ultra fast liquid chromatography-tandem mass spectrometry

Major depressive disorder is a severe, life-threatening and highly prevalent psychiatric disorder. A high percentage of people suffering from depression are characterized by hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in plasma glucocorticoid (cortisol in human and corticosterone in rodent) elevations. Glucocorticoid is a critical molecule in the onset of pathology of depression. A simple, highly sensitive and specific method based on ultra-fast liquid chromatography-tandem mass spectrometry method has been developed for the quantitation of corticosterone in mouse plasma for the first time, which provides technical support for the high-throughput measurement for clinical determination of corticosterone in biological samples. Samples were spiked with methanol to precipitate the protein, and then chromatographed on an Agilent Zorbax Eclipse Plus C18 (100 × 2.1 mm,1.8 µm) column by linear gradient elution with methanol and 0.1% formic acid as the mobile phase within 5 min. The detection of corticosterone was performed on ultra-fast liquid chromatography-triple quadrupole tandem mass spectrometry in the positive ion. The ions [M + H](+) m/z 347.2 → m/z 311.1 for corticosterone and [M + H](+) m/z 363.2 → m/z 327.2 for hydrocortisone (internal standard) were used for quantitative determination. The lower quantification limit for corticosterone was 1 ng/mL. The validated method was successfully applied to the quantitation of corticosterone in mouse plasma.