Development, validation and utilization of a highly sensitive LC-MS/MS method for quantification of levonorgestrel released from a subdermal implant in human plasma

Lauren R. Cirrincione, Sujan Dilly Penchala, Kimberly K Scarsi, Anthony T Podany, Lee C. Winchester, David J. Back, Saye H. Khoo, Courtney V Fletcher, Marco Siccardi, Laura J. Else

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Levonorgestrel (LNG) is a synthetic progestin that is available in oral contraceptive tablets, a subdermal implant, and an intrauterine system for contraception. LNG pharmacokinetics are a pivotal determinant of contraceptive efficacy and essential in assessing drug-drug interactions influencing LNG exposure following different routes of LNG administration. A highly sensitive LC-MS/MS method was developed and validated to quantify levonorgestrel in human plasma. Liquid-liquid extraction was utilized with a sample volume of 500 μL to extract levonorgestrel from plasma. Chromatographic separation of LNG was achieved with a Fortis™ C18 (3 μm: 100 mm × 2.1 mm) reverse phase analytical column. The mobile phases consisted of de-ionized water plus 0.1% NH4OH (100:0.1%, v/v) (A), and methanol plus 0.1% NH4OH (100:0.1%, v/v) (B) delivered as a gradient at a flow rate of 400 μL/min. Detection of LNG and internal standard (D-(−)-norgestrel-d7) was achieved using positive polarity mode monitoring at 313.2–245.2 amu and 320.1–251.2 amu, respectively. The assay was linear over the calibration range of 49.6 to 1500 pg/mL. This method was used to quantify plasma LNG released by subdermal implant in support of a drug interaction study among women with HIV receiving efavirenz- or nevirapine-based antiretroviral therapy.

Original languageEnglish (US)
Pages (from-to)106-112
Number of pages7
JournalJournal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Volume1084
DOIs
StatePublished - May 1 2018

Fingerprint

Plasma (human)
Levonorgestrel
Drug interactions
efavirenz
Drug Interactions
Progesterone Congeners
Plasmas
Nevirapine
Liquid-Liquid Extraction
Pharmacokinetics
Liquids
Oral Contraceptives
Contraceptive Agents
Contraception
Calibration
Tablets
Methanol
Assays
Flow rate
HIV

Keywords

  • LC-MS/MS
  • Levonorgestrel
  • Liquid-liquid extraction
  • Plasma
  • Subdermal implant

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry
  • Clinical Biochemistry
  • Cell Biology

Cite this

Development, validation and utilization of a highly sensitive LC-MS/MS method for quantification of levonorgestrel released from a subdermal implant in human plasma. / Cirrincione, Lauren R.; Penchala, Sujan Dilly; Scarsi, Kimberly K; Podany, Anthony T; Winchester, Lee C.; Back, David J.; Khoo, Saye H.; Fletcher, Courtney V; Siccardi, Marco; Else, Laura J.

In: Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, Vol. 1084, 01.05.2018, p. 106-112.

Research output: Contribution to journalArticle

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AU - Penchala, Sujan Dilly

AU - Scarsi, Kimberly K

AU - Podany, Anthony T

AU - Winchester, Lee C.

AU - Back, David J.

AU - Khoo, Saye H.

AU - Fletcher, Courtney V

AU - Siccardi, Marco

AU - Else, Laura J.

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