Detection of D-Dopa in Levodopa Tablets by Derivatization Coupled with LC-MS/MS
Chiral impurity analysis presents significant challenges due to limitations of detection methods. Levodopa (L-Dopa) is the primary medication for Parkinson's disease treatment for over 50 years. However, the detection of its chiral impurity is difficult due to the similarity of polarity. This study presents a novel analytical method for the quantitative detection of trace amount of D-Dopa, as well as other three impurities. The method demonstrated excellent chromatographic resolution for D-Dopa and L-Dopa (resolution = 4.15) and achieved a derivatization efficiency of 97% using a chlorine-labeled chiral probe (D-BPCl) for chemical derivatization, followed by analysis with liquid chromatography-tandem mass spectrometry (LC-MS/MS) on a conventional C18 column. Meanwhile, D-BPCl showed strong chiral selectivity on D-Dopa, and the ratio of mass spectrometric response for labeled D-Dopa to that of L-enantiomers was 2.78-fold under the same condition. The developed method demonstrates high sensitivity with detection limits of 7.88 μ g L -1 for D-Dopa, and 9.85 μ g L -1 for L-Dopa, with good linearity for every analyte (R 2 > 0.99), recoveries ranging from 94.1% to 106.8%, and high repeatability with relative standard deviation (RSD) values predominantly below 5%. Then the method was applied to analyze fifteen batches of levodopa tablets from five manufacturers. D-Dopa was successfully detected with the corresponding content ranging from 0.15% to 0.44%, which suggests that D-Dopa are more likely generated during the production process. The study underscores the significant safety concerns regarding Dopa-containing medications.
危险品化学品经营许可证（带存储）