Determination of Mildronate in Human Plasma and Urine by UPLC–Positive Ion Electrospray Tandem Mass Spectrometry
2011
A simple, rapid, and selective method to determine the concentration of mildronate in human plasma and urine using ultra performance liquid chromatography–tandem mass spectrometry (UPLC-MS-MS) was developed and validated. The detection was performed on a triple-quadrupole tandem mass spectrometer by multiple reaction monitoring mode via electrospray ionization at m/z 147.2–58.0 for mildronate and m/z 147.2–87.8 for the internal standard, carbachol. The UPLC separation was carried out with a UPLC BEH HILIC column. The mobile phase consisted of 0.08% formic acid in 30 mM ammonium acetate solution and acetonitrile (23:77, v/v). Plasma samples were extracted from plasma by protein precipitation and urine samples were diluted with the mobile phase. The analysis time was 3.5 min for each sample. Linear calibration curves ranged from 0.10 to 100.00 μg mL−1 in human plasma and 0.50 to 600.00 μg mL−1 in urine. The method had been successfully applied to a pharmacokinetic study in healthy volunteers. After single intravenously administration of 250, 500, and 750 mg mildronate, the elimination half-life (t 1/2) were (2.74 ± 0.67), (4.86 ± 0.82) and (5.16 ± 0.77) h, respectively. The t 1/2 for the 250 mg dose did vary significantly with other dosages (P < 0.05), mildronate may have non-linear pharmacokinetics in humans.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
8
References
8
Citations
NaN
KQI