Determination of newly synthesized lipoic acid-niacin dimer in rat plasma by UPLC/electrospray ionization tandem mass spectrometry: assay development, validation and application to a pharmacokinetic study.
A simple, sensitive and specific ultra-performance liquid chromatography/tandem mass spectrometry (UPLC-MS/MS) method was developed to determine the newly synthesized compound lipoic acid-niacin dimer (N2L) in plasma. Plasma samples were precipitated by methanol using tetrahydropalmatine as internal standard. Chromatographic separation was achieved on an Acquity BEH C18 (2.1 × 50 mm i.d., 1.7 µm) column; the mobile phase contains methanol and buffer solution (water with 0.5% formic acid and 10 mmol/L ammonium acetate). Multiple reaction monitoring (m/z 353.9 → 148.6 for N2L and m/z 356.0 → 192.0 for internal standard) was performed for detection and quantification. The method was validated to be rapid, specific, accurate and precise over the concentration range of 1-750 ng/mL; N2L was not stable on the bench-top or during freeze-freeze-thaw cycles in plasma, but was stable in the stock solution and after preparation in the autosampler for 24 h. The utility of the assay was confirmed by pharmacokinetic study of N2L in rats.
School of Pharmaceutical Sciences, Sun Yat-sen University, 132 Waihuan Road East, Guangzhou 510006 Higher Education Mega Center, Guangzhou, China.
Xiao
X
Chen
Jingwen
J
Gao
Yiming
Y
Jiang
Ping
P
Huang
Yuhui
Y
Xie
Rongbiao
R
Pi
Shuzhen
S
Zhu
Meicun
M
Yao
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D008297:Male; D009525:Niacin / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D051381:Rats; D017208:Rats, Wistar; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D053719:Tandem Mass Spectrometry / Q000379:methods; D008063:Thioctic Acid / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics
D009525:Niacin; D008063:Thioctic Acid
UPLC-MS/MS; lipoic acid-niacin dimer; pharmacokinetic study; validation