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采用液相色谱-串联质谱法同时定量检测人血清中的多种避孕激素。

Simultaneous quantitation of multiple contraceptive hormones in human serum by LC-MS/MS.

作者信息

Blue Steven W, Winchell Andrea J, Kaucher Amy V, Lieberman Rachel A, Gilles Christopher T, Pyra Maria N, Heffron Renee, Hou Xuanlin, Coombs Robert W, Nanda Kavita, Davis Nicole L, Kourtis Athena P, Herbeck Joshua T, Baeten Jared M, Lingappa Jairam R, Erikson David W

机构信息

Endocrine Technologies Support Core, Oregon National Primate Research Center, Beaverton, OR.

Shimadzu Scientific Instruments, Columbia, MD.

出版信息

Contraception. 2018 Apr;97(4):363-369. doi: 10.1016/j.contraception.2018.01.015. Epub 2018 Jan 31.

DOI:10.1016/j.contraception.2018.01.015
PMID:29407362
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5840044/
Abstract

OBJECTIVE

The objective was to develop a method to simultaneously quantify five commonly used hormonal contraceptives (HCs) and two endogenous sex steroids by liquid chromatography-tandem triple quadrupole mass spectrometry (LC-MS/MS) and apply this method to human serum samples.

STUDY DESIGN

We developed a method to simultaneously analyze ethinyl estradiol (EE2), etonogestrel (ENG), levonorgestrel (LNG), medroxyprogesterone acetate (MPA) and norethisterone (NET), along with estradiol (E2) and progesterone (P4), in human serum for a Shimadzu Nexera-LCMS-8050 LC-MS/MS platform. We analyzed serum collected from women self-reporting use of oral contraceptives, contraceptive implants or injectable contraceptives (n=14) and normally cycling women using no HC (n=15) as well as pooled samples from women administered various HCs (ENG, n=6; LNG, n=14; MPA, n=7; NET, n=5).

RESULTS

Limits of quantitation were 0.010ng/mL for E2, EE2 and P4; 0.020ng/mL for ENG, LNG and MPA; and 0.040ng/mL for NET. Precisions for all assays, as indicated by coefficient of variation, were less than or equal to 12.1%. Accuracies for all assays were in the range of 95%-108%. Endogenous hormone values obtained from analysis of human serum samples are in agreement with levels previously reported in the literature for normally cycling women as well as for women taking the appropriate HC.

CONCLUSIONS

We have developed a robust, accurate and sensitive method for simultaneously analyzing commonly used contraceptive steroids and endogenous sex steroids in human serum.

IMPLICATIONS

This analytical method can be used for quantitating contraceptive steroid levels in women for monitoring systemic exposure to determine drug interactions, nonadherence, misreporting and proper dosing.

摘要

目的

本研究旨在开发一种通过液相色谱 - 串联三重四极杆质谱法(LC-MS/MS)同时定量五种常用激素避孕药(HCs)和两种内源性甾体激素的方法,并将该方法应用于人体血清样本。

研究设计

我们开发了一种方法,可在岛津Nexera-LCMS-8050 LC-MS/MS平台上同时分析人体血清中的炔雌醇(EE2)、依托孕烯(ENG)、左炔诺孕酮(LNG)、醋酸甲羟孕酮(MPA)和炔诺酮(NET),以及雌二醇(E2)和孕酮(P4)。我们分析了自我报告使用口服避孕药、避孕植入剂或注射用避孕药的女性(n = 14)以及未使用任何激素避孕药的正常月经周期女性(n = 15)采集的血清,以及接受各种激素避孕药(ENG,n = 6;LNG,n = 14;MPA,n = 7;NET,n = 5)的女性的混合样本。

结果

E2、EE2和P4的定量限为0.010ng/mL;ENG、LNG和MPA的定量限为0.020ng/mL;NET的定量限为0.040ng/mL。所有检测的精密度(以变异系数表示)均小于或等于12.1%。所有检测的准确度在95% - 108%范围内。通过分析人体血清样本获得的内源性激素值与文献中先前报道的正常月经周期女性以及服用相应激素避孕药的女性的水平一致。

结论

我们开发了一种强大、准确且灵敏的方法,用于同时分析人体血清中常用的避孕甾体激素和内源性甾体激素。

意义

这种分析方法可用于定量女性体内的避孕甾体激素水平,以监测全身暴露情况,从而确定药物相互作用、不依从性、误报和正确剂量。

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