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Anal Chem. 2016 Jan 19;88(2):1336-44. doi: 10.1021/acs.analchem.5b03794. Epub 2015 Dec 30.

Analysis of Antiretrovirals in Single Hair Strands for Evaluation of Drug Adherence with Infrared-Matrix-Assisted Laser Desorption Electrospray Ionization Mass Spectrometry Imaging.

Author information

1
Eshelman School of Pharmacy, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
2
W.M. Keck FTMS Laboratory for Human Health Research, Department of Chemistry, North Carolina State University , Raleigh, North Carolina 27695, United States.
3
School of Medicine, University of North Carolina , Chapel Hill, North Carolina 27599, United States.
4
Center for AIDS Research, University of North Carolina , Chapel Hill, North Carolina 27599, United States.

Abstract

Adherence to a drug regimen can be a strong predictor of health outcomes, and validated measures of adherence are necessary at all stages of therapy from drug development to prescription. Many of the existing metrics of drug adherence (e.g., self-report, pill counts, blood monitoring) have limitations, and analysis of hair strands has recently emerged as an objective alternative. Traditional methods of hair analysis based on LC-MS/MS (segmenting strands at ≥1 cm length) are not capable of preserving a temporal record of drug intake at higher resolution than approximately 1 month. Here, we evaluated the detectability of HIV antiretrovirals (ARVs) in hair from a range of drug classes using infrared matrix-assisted laser desorption electrospray ionization (IR-MALDESI) mass spectrometry imaging (MSI) with 100 μm resolution. Infrared laser desorption of hair strands was shown to penetrate into the strand cortex, allowing direct measurement by MSI without analyte extraction. Using optimized desorption conditions, a linear correlation between IR-MALDESI ion abundance and LC-MS/MS response was observed for six common ARVs with estimated limits of detection less than or equal to 1.6 ng/mg hair. The distribution of efavirenz (EFV) was then monitored in a series of hair strands collected from HIV infected, virologically suppressed patients. Because of the role hair melanin plays in accumulation of basic drugs (like most ARVs), an MSI method to quantify the melanin biomarker pyrrole-2,3,5-tricarboxylic acid (PTCA) was evaluated as a means of normalizing drug response between patients to develop broadly applicable adherence criteria.

PMID:
26688545
PMCID:
PMC5301654
DOI:
10.1021/acs.analchem.5b03794
[Indexed for MEDLINE]
Free PMC Article

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