Organic Solvents Compromise Performance of Internal Standard (Ascomycin) in Proficiency Testing of Mass Spectrometry-Based Assays for Tacrolimus

Abstract

Therapeutic drug monitoring of immunosuppressive agents by liquid chromatography (LC) coupled with mass spectrometry (MS) can provide highly selective and sensitive quantification from biological fluids. Interlaboratory performance for cyclosporine, tacrolimus, and sirolimus, as assessed by LC/MS, in proficiency testing (PT) programs [e.g., College of American Pathologists (CAP) (1) and the International Proficiency Testing Scheme (IPTS) (2)] has been poor, albeit improving, although individual laboratories report excellent interassay imprecision (CV <5.5%) at drug concentrations across analytical ranges (3)(4)(5)(6). Lack of industry-wide standardization may contribute to variations in PT program performance across MS laboratories because it requires that those laboratories develop “home brew” assays, use reference materials with potentially different purities obtained from numerous sources, and prepare either whole-blood calibrator/quality-control (QC) materials in house or purchase commercial materials that may be verified only for a specific procedure. In addition, most PT samples are unlike routine specimens, being prepared from either artificial or whole-blood–like matrices (sometimes pooled patient blood) that are subjected to the rigors of batch preparation and shipping. I describe here an experience of specific and unusual performance of PT samples, which likely resulted from instabilities of the internal …