Department of Molecular and Cell Biology, University of Cape, Cape Town, South Africa.
Department of Molecular and Cell Biology, University of Cape, Cape Town, South Africa; Institute of Infectious Disease and Molecular Medicine, University of Cape Town, South Africa.
Steroids. 2022 Nov;187:109100. doi: 10.1016/j.steroids.2022.109100. Epub 2022 Aug 12.
Quantification of serum progestin levels in clinical contraceptive studies is now routinely performed to understand progestin pharmacokinetics and to correct for unreliable self-reporting of contraceptive use by study participants. Many such studies are focussed on the three-monthly progestin-only intramuscular (IM) injectable contraceptive depot medroxyprogesterone acetate (DMPA-IM). Methods commonly used to measure serum MPA levels include liquid chromatography coupled to mass spectrometry (LC/MS) and radioimmunoassay (RIA); however, RIA methods have not been used in recent years. We review the available literature and find that these methods vary widely in terms of use of organic solvent extraction, use of derivitization and choice of organic solvent and chromatography columns. There is a lack of standardization of LC/MS methodology, including a lack of detailed extraction protocols. Limited evidence suggests that RIA, without organic solvent extraction, likely over-estimates progestin levels. Maximum MPA concentrations in the first two weeks post-injection show wide inter-individual and inter-study variation, regardless of quantification method used. Standardization of quantification methods and sampling time post-injection is required to improve interpretation of clinical data, in particular the side effects arising at different times depending on the pharmacokinetic profile unique to injectable contraceptives.
在临床避孕研究中，目前通常会定量检测血清孕激素水平，以了解孕激素的药代动力学，并纠正研究参与者对避孕措施使用情况不可靠的自我报告。许多此类研究都集中在每三个月注射一次的孕激素仅有的肌肉内（IM）注射避孕药物醋酸甲羟孕酮（DMPA-IM）上。用于测量血清 MPA 水平的常用方法包括液相色谱-质谱联用（LC/MS）和放射免疫测定（RIA）；然而，近年来并未使用 RIA 方法。我们回顾了现有文献，发现这些方法在有机溶剂萃取、衍生化的使用以及有机溶剂和色谱柱的选择方面存在很大差异。LC/MS 方法缺乏标准化，包括缺乏详细的提取方案。有限的证据表明，未经有机溶剂萃取的 RIA 可能会高估孕激素水平。注射后前两周的 MPA 最大浓度表现出广泛的个体间和研究间差异，无论使用何种定量方法。需要对定量方法和注射后采样时间进行标准化，以改善对临床数据的解释，特别是根据独特的注射避孕药的药代动力学特征，在不同时间出现的副作用。
