[Determination of levosimendan and its main metabolites in human plasma with HPLC-MS/MS method].
This paper is aimed to develop rapid, sensitive and convenient HPLC-MS/MS methods for the quantification of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma. According to the different natures of the compounds, two sets of liquid chromatography and ionization modes were used for determination the concentration of levosimendan and its metabolites OR-1855 and OR-1896 in human plasma, separately. Following protein precipitation with methanol, the levosimendan and internal standard (rosuvastatin) were separated on a Capcell MG III C18 column (35 mm x 2.0 mm ID, 3 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (55: 45: 0.02, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated in the negative ion mode. Its metabolites OR-1855, OR-1896 and internal standard doxofylline were extracted from plasma by liquid-liquid extraction with ethyl acetate. Chromatographic separation was performed on a Zorbax Extend C18 column (150 mm x 4.6 mm ID, 5 microm) with the mobile phase consisted of methanol-15 mmol x L(-1) ammonium acetate-formic acid (65 :35 :0.1, v/v/v). A tandem mass spectrometer equipped with electrospray ionization source was used as the detector and operated at the positive ion mode. The linear concentration ranges of the calibration curves for levosimendan and OR-1855 and OR-1896 were 0.10-50.0 ng x mL(-1), 0.20-100 ng x mL(-1), 0.20-100 ng x mL(-1), respectively. The lower limits of quantification of levosimendan and OR-1855 and OR-1896 were 0.10 ng x mL(-1), 0.20 ng x mL(-1), 0.20 ng x mL(-1), respectively. The methods proved to be sensitive, simple and rapid, and suitable for the pharmacokinetic study of levosimendan injection.
Li
Shao-rong
SR
Zhejiang University of Technology, Hangzhou 310014, China.
Chen
Xiao-yan
XY
Zhang
Yi-fan
YF
Li
Guo-xin
GX
Jiang
Chun-mei
CM
Zhong
Da-fang
DF
D000081:Acetamides / Q000097:blood*; D002316:Cardiotonic Agents / Q000097:blood / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D006801:Humans; D006835:Hydrazones / Q000097:blood* / Q000378:metabolism*; D008297:Male; D011724:Pyridazines / Q000097:blood* / Q000378:metabolism*; D000077464:Simendan; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods
D000081:Acetamides; D002316:Cardiotonic Agents; D006835:Hydrazones; C414222:N-(4-(4-methyl-6-oxo-1,4,5,6-tetrahydropyridazin-3-yl)phenyl)acetamide; D011724:Pyridazines; D000077464:Simendan