Development of sensitive derivatization method for aldosterone in liquid chromatography-electrospray ionization tandem mass spectrometry of corticosteroids.
A highly sensitive quantification method of aldosterone by liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) was investigated in a positive mode using recently developed picolinyl derivatization. Aldosterone was smoothly and quantitatively converted to the ethyl ether-picolinyl derivative by treatment with HCl-ethanol followed by the esterification with picolinic acid in the presence of 2-methyl-6-nitrobenzoic anhydride and 4-dimethylaminopyridine. The positive ion-ESI mass spectrum of the ethyl ether-picolinyl derivative was characterized by an appearance of protonated molecule ([M+H](+)) as a base peak. The ethyl ether-picolinyl derivatization gave a successful result in a separation of aldosterone from corticosterone, dehydrocorticosterone and cortexolone, and also provided an approximately 10-fold higher ESI response in the positive-LC-ESI-MS/MS (selected reaction monitoring; SRM) when compared to that of underivatized molecule (negative mode). The limit of quantification of aldosterone by SRM using ethyl ether-picolinyl derivatization (m/z 494-->m/z 448) was 1 pg/0.2 ml serum with accuracy and precision of 92.6% and 5.6%, respectively.
Yamashita
Kouwa
K
Faculty of Pharmaceutical Science, Tohoku Pharmaceutical University, 4-1 Komatsushima 4-Chome, Aoba-ku, Sendai, Miyagi 981-8558, Japan. kyama@tohoku-pharm.ac
Okuyama
Mitsunobu
M
Nakagawa
Risa
R
Honma
Seijiro
S
Satoh
Fumitoshi
F
Morimoto
Ryo
R
Ito
Sadayoshi
S
Takahashi
Madoka
M
Numazawa
Mitsuteru
M
D000305:Adrenal Cortex Hormones / Q000097:blood / Q000737:chemistry*; D000450:Aldosterone / Q000097:blood / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D000431:Ethanol / Q000737:chemistry; D006801:Humans; D006851:Hydrochloric Acid / Q000737:chemistry; D015394:Molecular Structure; D010848:Picolinic Acids / Q000737:chemistry; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods*
D000305:Adrenal Cortex Hormones; D010848:Picolinic Acids; D000431:Ethanol; D000450:Aldosterone; D006851:Hydrochloric Acid; C030614:picolinic acid