Clinical application of an optimized reference measurement procedure for serum digoxin using bracketing calibration...

Area of Science:

• Clinical Chemistry
• Analytical Chemistry
• Mass Spectrometry

Background:

• Digoxin is vital for cardiovascular disease treatment but requires precise blood concentration monitoring due to its narrow therapeutic range.
• Current clinical methods for digoxin measurement may lack standardization, potentially impacting patient care.
• A robust reference measurement procedure (RMP) is essential for ensuring accuracy and comparability of digoxin results.

Purpose of the Study:

• To optimize and validate an ID-LC-MS/MS based RMP for serum digoxin measurement.
• To evaluate the performance characteristics of the optimized RMP, including accuracy, precision, and linearity.
• To assess the need for standardization by comparing the RMP with existing clinical systems.

Main Methods:

• Optimization of sample pre-treatment and detection processes for ID-LC-MS/MS.
• Implementation of a bracketing calibration method for enhanced accuracy, especially at extreme concentrations.
• Performance evaluation including limit of detection (LoD), limit of quantification (LLoQ), imprecision, recovery, linearity, and bias assessment against external quality assessment schemes.

Main Results:

• The optimized RMP demonstrated excellent performance with LoD of 0.05 ng/mL and LLoQ of 0.10 ng/mL.
• High precision with intra- and inter-assay imprecisions below 2.51% and low bias (0.41% and 2.00% compared to reference labs).
• Significant differences observed among clinical systems in a verification plan, underscoring the need for standardization; good correlation with immunoassay methods confirmed feasibility.

Conclusions:

• The optimized ID-LC-MS/MS RMP provides an accurate and reliable baseline for serum digoxin measurement.
• This RMP is crucial for enhancing the accuracy and precision of routine clinical digoxin assays.
• Standardization efforts are necessary to improve the comparability of digoxin measurements across different clinical laboratories.