A quantitative analytical method for PIVKA-II using multiple reaction monitoring-mass spectrometry for early diagnosis of hepatocellular carcinoma

作者：Sohn Areum; Kim Hyunsoo; Yu Su Jong; Yoon Jung Hwan; Kim Youngsoo^*

来源：Analytical and Bioanalytical Chemistry, 2017, 409(11): 2829-2838.

DOI：10.1007/s00216-017-0227-8

• Multiple ReactionMonitoring (MRM)
• Mass spectrometry
• Hepatocellularcarcinoma(HCC)
• Prothrombin induced by vitamin K absence-II (PIVKA-II)
• Absolute quantification

Prothrombin induced by vitamin K absence-II (PIVKA-II) is an effective tumor marker for hepatocellular carcinoma (HCC). We have developed a novel targeted mass spectrometric (MS) assay for quantifying PIVKA-II in human serum. The ideal signature peptide was selected to measure PIVKA-II concentrations on a triple quadrupole (QqQ) mass spectrometer, and the chromatography gradient was optimized for the peptide separation to minimize elution interference. Using multiple reaction monitoring-mass spectrometry (MRM-MS), good linearity (R-2 = 0.9988) was obtained for PIVKA-II over a range of 3 orders. We achieved a limit of detection (LOD) of 0.45 nM (31.72 ng/mL), a limit of quantification (LOQ) of 0.93 nM (65.31 ng/mL), a lower limit of quantification (LLOQ) of 0.49 nM (34.32 ng/mL), and an upper limit of quantification (ULOQ) of 1000.00 nM (70,037.00 ng/mL). The intra-day and inter-day precisions were within +/- 14.96%, and the accuracy ranged from 87.66 to 114.29% for QC samples at four concentrations. Compared with an established immunoassay, the correlation (R = 0.8335) was good for the measurements of PIVKA-II concentrations. This method was successfully applied to the analysis of clinical samples for normal control (n = 50), chronic hepatitis (n = 50), liver cirrhosis (n = 50), HCC(n = 50), and recovery (n = 50) serum.

• 出版日期2017-4
• 单位河北医科大学