As the most common form of dementia, Alzheimer's disease (AD) comprises 60–80 % of all dementia cases. The overall age- and sex-adjusted prevalence of AD is estimated to be 3.9 % (3.8–4.1 %) in China [1]. The β-amyloid 1-42 (Aβ1-42) and Aβ1-40 in cerebrospinal fluid (CSF) are important in the early and differential diagnosis of AD [2] and could be used to guide patient management, particularly in atypical and clinically challenging cases [3]. The Alzheimer's Association external quality control (AAQC) program found that Lumipulse G fully automated chemiluminescence detection is currently the most used assay for the measurement of CSF Aβ1-42 and Aβ1-40; however, the measurements from different laboratories based on different assays and even same assays cannot be readily compared [4]. Under this circumstances, it is difficult to establish generally applicable cutoff values, which largely restricts the wider usage of these core biomarkers in routine clinical practice. This phenomenon is closely related to the lack of measurement harmonization and standardization.

Because it can accurately quantify target analytes in complex matrixes, liquid chromatography–tandem mass spectrometry (LC–MS/MS) is considered a suitable technology for achieving measurement standardization in clinical practice [5]. Moreover, LC–MS/MS overcomes the disadvantages of immunoassays, including the requirements for specific antibodies and reagents, narrow linear ranges, cross-reactivity among peptides, and batch-to-batch variability [6]. LC–MS/MS assays of CSF Aβ1-42 and Aβ1-40 have been developed [7,8], and candidate reference measurement procedures have been launched [9,10]. However, these LC–MS/MS assays used common solid-phase extraction (SPE) technology to extract, purify, and concentrate the target analytes, requiring complex labor-intensive operations, and are thus hardly used in clinical practice. Although fully automated SPE technology has been developed to detect some analytes, such as catecholamines, in plasma and urine samples, the traditional SPE plate-based automated assay is not very flexible with usually fixed 96-tests setting on one plate [11]. To overcome these limitations, a new sample preparation technique based on SPE-analogous magnetic beads was developed [12,13]. Similar to the working principle of automated clinical chemistry or immunoanalyzer systems, these free-moving magnetic beads can be easily distributed or transferred under the control of a magnetic bar, allowing for flexible automation.

The aims of this study were to (1) establish and verify a robust ultra-performance LC-MS/MS (UPLC–MS/MS) method based on a novel automated magnetic-bead-assisted sequential extraction (MBASE) technology to simultaneously determine Aβ1-42 and Aβ1-40 in CSF and (2) compare the analytical performance of this method with that of the traditional SPE UPLC–MS/MS method and evaluate the measurement consistency between this method, SPE UPLC-MS/MS method, and Lumipulse G fully automated chemiluminescence detection system.