Validation and Clinical Evaluation of an LC-MS/MS Method for Serum Full-Length Parathyroid Hormone 1-84 with Application to Chronic Kidney Disease.

Objective: Accurate measurement of full-length parathyroid hormone (PTH) 1-84 is important for evaluating disorders of calcium-phosphate metabolism, particularly in chronic kidney disease (CKD). Because immunoassay results may vary according to assay design and analyte recognition, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for selective quantification of serum PTH 1-84 and explored its potential clinical relevance in kidney-related disease. Methods: Serum samples were processed by solid-phase extraction and spiked with an isotope-labeled internal standard. PTH 1-84 was separated on a C4 column and detected in positive electrospray ionization mode using multiple reaction monitoring. Analytical performance, including selectivity, linearity, accuracy, precision, recovery, and matrix effect, was evaluated using predefined acceptance criteria. A retrospective clinical analysis was then performed to compare this method with chemiluminescent immunoassay (CLIA) and to assess associations with calcium-phosphate metabolism markers. Results: The assay showed satisfactory analytical performance with negligible matrix effect and no meaningful interference under the tested conditions. In uremic patients, PTH concentrations measured by LC-MS/MS were generally lower than those obtained by CLIA, although the two methods remained correlated. PTH 1-84 measured by LC-MS/MS showed a stronger association with serum phosphate than with serum calcium in this cohort. In patients with renal involvement, both methods showed higher PTH concentrations than in patients without renal involvement. Conclusion: This LC-MS/MS assay provides selective quantification of serum full-length PTH 1-84 with satisfactory analytical performance. It may serve as an orthogonal analytical approach for studies of mineral metabolism in CKD-related disease, although intermethod differences should be interpreted cautiously.