Development, validation and clinical application of a novel method for the quantification of efavirenz in dried breast milk spots using LC-MS/MS


Olagunju, A ORCID: 0000-0002-6588-5749, Bolaji, OO, Amara, A ORCID: 0000-0002-1137-2948, Waitt, C ORCID: 0000-0003-0134-5855, Else, L, Soyinka, J, Adeagbo, B, Adejuyigbe, E, Siccardi, M ORCID: 0000-0002-3539-7867, Back, D et al (show 2 more authors) (2015) Development, validation and clinical application of a novel method for the quantification of efavirenz in dried breast milk spots using LC-MS/MS Journal of Antimicrobial Chemotherapy, 70 (2). pp. 555-561. ISSN 0305-7453, 1460-2091

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Abstract

Objectives: This manuscript describes the development, validation and clinical application of a novel method for the quantification of the antiretroviral drug efavirenz in dried breast milk spots using LC-MS. Methods: Dried breast milk spots were prepared by spotting 30 μL of human breast milk on each circle of Whatman 903 Protein Saver cards. Chromatographic separation was achieved on a reverse-phase C18 column with 1 mM ammonium acetate in water/acetonitrile using a solvent gradient at a flow rate of 400 μL/min and detection was by TSQ Quantum Access triple quadrupole mass spectrometer equipped with a heated electrospray ionization source. The method was applied to characterize the breast milk pharmacokinetic profile of efavirenz in HIV-positive nursing mothers receiving regimens containing 600 mg of efavirenz once daily. Results: The assay was validated over the concentration range 50-7500 ng/mL. Accuracy ranged between 95.2% and 102.5% and precision ranged between 1.05% and 9.53%. The average recovery of efavirenz from dried breast milk spots was 106.4% and the matrix effect was 8.14%. Stability of efavirenz in dried breast milk spots and processed samples at room temperature, -40°C and -80°C was demonstrated. In the pharmacokinetic study, the mean (SD) AUC<inf>0-24</inf>, C<inf>max</inf> and C<inf>min</inf> of efavirenz in breast milk were 59620 ng·h/mL (17440), 4527 ng/mL (1767) and 1261 ng/mL (755.9), respectively. The mean (range) milk-to-plasma concentration ratio over the dosing interval was 0.78 (0.57-1.26). Conclusions: The dried breast milk spot method is simple, robust, accurate and precise, and can be used in settings with limited resources.

Item Type: Article
Uncontrolled Keywords: liquid chromatography, mass spectrometry, antiretroviral
Depositing User: Symplectic Admin
Date Deposited: 21 May 2015 15:18
Last Modified: 01 Mar 2026 00:40
DOI: 10.1093/jac/dku420
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URI: https://livrepository.liverpool.ac.uk/id/eprint/2003720
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