Determination of alprostadil in rat plasma by ultra performance liquid chromatography-electrospray ionization-tandem mass spectrometry after intravenous administration.
A rapid, highly selective ultra performance liquid chromatography-electrospray ionisation-tandem mass spectrometry method (UPLC-ESI-MS/MS) was developed and validated for the determination and pharmacokinetic investigation of alprostadil in rat plasma. After a simple sample preparation procedure involving a one-step liquid-liquid extraction, alprostadil and the internal standard, diphenhydramine, were chromatographed on an ACQUITY UPLC BEH C(18) column with gradient elution using a mobile phase consisting of acetonitrile and water (containing 0.1% formic acid) at a flow rate of 0.25 mL min(-1). The detection was performed on a triple quadrupole tandem mass spectrometer in multiple reaction monitoring (MRM) mode via an electrospray ionization (ESI) source. The calibration curve was linear (r(2)=0.99) over the concentration range 0.4-250.0 ng mL(-1), with a lower limit of quantification of 0.4 ng mL(-1) for alprostadil. The inter- and intra-day precision (%R.S.D.) was less than 8.5% and 2.4%, respectively, and the accuracy (RE%) was between 9.3% and 1.0% (n=6). Alprostadil in rat plasma was stable when stored at room temperature for 0.5h and at -20 degrees C for two weeks. The method was very rapid, simple and reliable, and was employed for the first time for the pharmacokinetic studies of alprostadil in rats after a single intravenous administration of 50 microg kg(-1).
Lin
Xia
X
Department of Pharmaceutics, Shenyang Pharmaceutical University, Shenyang, PR China.
Zhang
Yu
Y
Cui
Yue
Y
Wang
Lin
L
Wang
Jing
J
Tang
Xing
X
D000527:Alprostadil / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics; D000818:Animals; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D007202:Indicators and Reagents; D007275:Injections, Intravenous; D008297:Male; D011786:Quality Control; D051381:Rats; D017208:Rats, Wistar; D012015:Reference Standards; D015203:Reproducibility of Results; D012997:Solvents; D013048:Specimen Handling; D021241:Spectrometry, Mass, Electrospray Ionization; D053719:Tandem Mass Spectrometry; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000097:blood* / Q000493:pharmacokinetics
D007202:Indicators and Reagents; D012997:Solvents; D014665:Vasodilator Agents; D000527:Alprostadil