Determination of raltitrexed in human plasma by high performance liquid chromatography-electrospray ionization-mass spectrometry.
A sensitive high performance liquid chromatography-electrospray ionization-mass spectrometry (HPLC-ESI-MS) assay was developed to determine raltitrexed in human plasma. After addition of benazeprilat as the internal standard (IS), methanol was used to produce a protein-free extract. Chromatographic separation was achieved with a Zorbax SB-C18 column (Narrow-Bore 2.1 mmx150 mm, 5-microm) using a mobile phase of acetonitrile-water containing 0.1% formic acid and 2% methanol (21.9:78.1, v/v). Raltitrexed was determined with electrospray ionization-mass spectrometry. HPLC-ESI-MS was performed in the selected ion monitoring (SIM) mode using target ions at [M+H]+ m/z 459.1 for raltitrexed and [M+H]+ m/z 397.1 for IS. Calibration curves were linear over the range of 2.0-3000 ng/ml. The lower limit of quantification was 2.0 ng/ml. The intra- and inter-batch variability values were less than 6.7% and 10.3%, respectively. The mean plasma extraction recovery of raltitrexed was in the range of 85.2-91.1%. The method was successfully applied to determine the plasma concentrations of raltitrexed in eight Chinese colorectal cancer patients.
Hu
Jingjing
J
Department of Pharmaceutical Analysis, China Pharmaceutical University, and Department of Clinical Pharmacology, the 81st Hospital of Chinese PLA, Nanjing, China.
Ding
Li
L
Song
Qinxin
Q
Gao
Ying
Y
Qing
Shukui
S
D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D006801:Humans; D015394:Molecular Structure; D011799:Quinazolines / Q000097:blood* / Q000737:chemistry; D015203:Reproducibility of Results; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013876:Thiophenes / Q000097:blood* / Q000737:chemistry
D011799:Quinazolines; D013876:Thiophenes; C068874:raltitrexed