Abstract
Objectives: To compare performance characteristics of etonogestrel bioanalytical assays across laboratories. Study design: We conducted a blinded, six laboratory study: five academic laboratories and one contracted commercial laboratory (reference). Etonogestrel was quantitated at each laboratory in both prepared serum and/or plasma samples of six known etonogestrel concentrations, and in 60 clinical samples from participants using etonogestrel-containing contraceptive methods. Per regulatory guidance, laboratory accuracy (percent bias) and precision (coefficient of variation; CV) were defined as ±15% of the nominal prepared concentration. We compared inter- and intra-laboratory agreement using a Kendall's Tau-B and Passing-Bablok regression. Results: For prepared samples, six laboratories analyzed serum and three laboratories analyzed plasma. All etonogestrel results were within ±15% for accuracy across all concentrations at four labs, including the reference laboratory. All labs demonstrated high precision, with only one occurrence of CV >15%. We found a positive association between prepared plasma and serum etonogestrel results (Kendall's Tau-B 0.80–0.88). For clinical samples, five laboratories analyzed serum and three laboratories analyzed plasma. Compared to the reference laboratory, inter-laboratory serum etonogestrel concentrations were positively correlated (Kendall's Tau-B 0.76–0.95). Proportional bias was observed, meaning individual lab etonogestrel results were consistently higher (slope estimates 0.78–0.95) or lower (slope estimates 1.05–1.10) than the reference laboratory. In clinical samples, intra-laboratory results were well associated between plasma and serum (Kendall's Tau-B 0.92–0.96). Conclusions: There was good intra-laboratory agreement, irrespective of sample matrix; however, there was inter-laboratory variability in etonogestrel results. Differences between laboratory results should be considered when comparing etonogestrel pharmacokinetics across studies. Implications: Etonogestrel concentrations were highly precise within each laboratory and were comparable between serum and plasma. Results varied between laboratories (5–28% higher to 5–9% lower compared to the Organon commercial laboratory). To minimize variability, we recommend utilizing a single laboratory that conducts routine proficiency testing for etonogestrel analysis within a study.
Original language | English (US) |
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Article number | 110720 |
Journal | Contraception |
Volume | 142 |
DOIs | |
State | Published - Feb 2025 |
Keywords
- Accuracy
- Bioanalytic assay
- Etonogestrel
- Pharmacokinetics
- Precision
- Variability
ASJC Scopus subject areas
- Reproductive Medicine
- Obstetrics and Gynecology