Simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate in rat plasma by high-performance liquid chromatography-tandem mass spectrometry and its application in a pharmacokinetic study.
A sensitive, simple and rapid HPLC-MS/MS method has been developed and validated for the simultaneous determination of L-dopa and its prodrug (S)-4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate (AEPD) in rat plasma in the present study. The analytes were separated on a C(18) column (5 microm, 2.1 mm x 150 mm) with a security guard C(18) column (5 microm, 4 mm x 20 mm) and a triple-quadrupole mass spectrometry equipped with an electrospray ionization (ESI) source was applied for detection. With alpha-methyldopa as internal standard, sample pretreatment involved in a one-step protein precipitation with 0.4M perchloric acid. The method was linear over the concentration ranges of 50-5000 ng/ml for L-dopa and 12.5-2500 ng/ml for AEPD. The intra-day and inter-day relative standard deviations (RSD) were less than 15% and the relative errors (RE) were all within 15%. Finally, the method was successfully applied to support the pharmacokinetic study after L-dopa and its prodrug AEPD were orally administrated to the Sprague-Dawley rats, respectively.
School of Pharmaceutical, Guangxi Medical University, 22 Shuangyong Road, Nanning 530021, China.
Weizhe
W
Jiang
Li
L
Lv
Songyu
S
Zhou
Xingzhen
X
Huang
Xiaoxia
X
Shi
Cong
C
Lv
Lingling
L
Wu
Chongyao
C
Xu
D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D007980:Levodopa / Q000031:analogs & derivatives* / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D011355:Prodrugs / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D053719:Tandem Mass Spectrometry / Q000379:methods*
C552099:4-(2-acetamido-3-ethoxy-3-oxopropyl)-1,2-phenylene diacetate; D011355:Prodrugs; D007980:Levodopa