Development and validation of an expanded panel of progestins using liquid chromatography-tandem triple quadrupole mass spectrometry to monitor protocol compliance in hormonal contraceptive pharmacokinetic/pharmacodynamic studies

Abstract

We developed and validated the use of ultra-high-performance liquid chromatography–heated electrospray ionization-tandem triple quadrupole mass spectrometry to simultaneously analyze serum concentrations of ethinylestradiol, dienogest, norelgestromin, norethindrone, gestodene, levonorgestrel, etonogestrel, segesterone acetate, medroxyprogesterone acetate, and drospirenone. The calibration range for all targets was 0.009–10 ng/mL, with lower limit of quantification of 0.009 ng/mL for all analytes except gestodene (0.019 ng/mL). We used our assay to check compliance among participants in a clinical trial, confirmed the use of drospirenone in 11 of 13 study participants, and evidence of noncompliant progestins in 2 (levonorgestrel = 1, norethindrone = 1). We conclude that this approach provides an accurate method to check protocol compliance in contraceptive clinical trials. ImplicationsThe availability of a liquid chromatography-tandem triple quadrupole mass spectrometry multiprogestin analysis panel for simultaneous evaluation of the most common contraceptive steroids approved worldwide could improve monitoring of compliance and protocol adherence in clinical trials.