期刊
JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY
卷 70, 期 2, 页码 555-561出版社
OXFORD UNIV PRESS
DOI: 10.1093/jac/dku420
关键词
liquid chromatography; mass spectrometry; antiretroviral
资金
- HIV Research Trust, UK
- Wellcome Trust [104422/Z/14/Z] Funding Source: Wellcome Trust
- MRC [G0901364, G0800247] Funding Source: UKRI
- Academy of Medical Sciences (AMS) [AMS-SGCL8-Waitt] Funding Source: researchfish
- Medical Research Council [G0800247, G0901364] Funding Source: researchfish
- National Institute for Health Research [CL-2010-07-004] Funding Source: researchfish
- Wellcome Trust [104422/Z/14/Z] Funding Source: researchfish
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 mu L 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 mu L/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 degrees C and -80 degrees C was demonstrated. In the pharmacokinetic study, the mean (SD) AUC(0-24), C-max and C-min 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.
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