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PLoS One. 2016 May 18;11(5):e0155887. doi: 10.1371/journal.pone.0155887. eCollection 2016.

Quantifying Isoniazid Levels in Small Hair Samples: A Novel Method for Assessing Adherence during the Treatment of Latent and Active Tuberculosis.

Author information

1
Department of Obstetrics, Gynecology and Reproductive Sciences, University of California San Francisco (UCSF), San Francisco, CA, United States of America.
2
Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of California San Francisco (UCSF), San Francisco, CA, United States of America.
3
Department of Medicine, Division of HIV, Infectious Diseases, and Global Medicine, University of California San Francisco (UCSF), San Francisco, CA, United States of America.
4
Department of Epidemiology and Biostatistics, University of California San Francisco (UCSF), San Francisco, CA, United States of America.

Abstract

BACKGROUND:

Tuberculosis (TB) is the leading cause of death from an infectious pathogen worldwide and the most prevalent opportunistic infection in people living with HIV. Isoniazid preventive therapy (IPT) reduces the incidence of active TB and reduces morbidity and mortality in HIV-infected patients independently of antiretroviral therapy. However, treatment of latent or active TB is lengthy and inter-patient variability in pharmacokinetics and adherence common. Current methods of assessing adherence to TB treatment using drug levels in plasma or urine assess short-term exposure and pose logistical challenges. Drug concentrations in hair assess long-term exposure and have demonstrated pharmacodynamic relevance in HIV.

METHODS:

A large hair sample from a patient with active TB was obtained for assay development. Methods to pulverize hair and extract isoniazid were optimized and then the drug detected by liquid chromatography/ tandem mass spectrometry (LC/MS-MS). The method was validated for specificity, accuracy, precision, recovery, linearity and stability to establish the assay's suitability for therapeutic drug monitoring (TDM). Hair samples from patients on directly-observe isoniazid-based latent or active TB therapy from the San Francisco Department of Public Health TB clinic were then tested.

RESULTS:

Our LC/MS-MS-based assay detected isoniazid in quantities as low as 0.02ng/mg using 10-25 strands hair. Concentrations in spiked samples demonstrated linearity from 0.05-50ng/mg. Assay precision and accuracy for spiked quality-control samples were high, with an overall recovery rate of 79.5%. In 18 patients with latent or active TB on treatment, isoniazid was detected across a wide linear dynamic range.

CONCLUSIONS:

An LC-MS/MS-based assay to quantify isoniazid levels in hair with performance characteristics suitable for TDM was developed and validated. Hair concentrations of isoniazid assess long-term exposure and may be useful for monitoring adherence to latent or active TB treatment in the setting of HIV.

PMID:
27191185
PMCID:
PMC4871544
DOI:
10.1371/journal.pone.0155887
[Indexed for MEDLINE]
Free PMC Article

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