{'fraction_non_alphanumeric': 0.04496047430830039, 'fraction_numerical': 0.0291501976284585, 'mean_word_length': 5.25, 'pattern_counts': {'":': 0, '<': 0, '<?xml version=': 0, '>': 1, 'https://': 0, 'lorem ipsum': 0, 'www.': 0, 'xml': 0}, 'pii_count': 0, 'substrings_counts': 0, 'word_list_counts': {'cursed_substrings.json': 0, 'profanity_word_list.json': 0, 'sexual_word_list.json': 0, 'zh_pornsignals.json': 0}}
Simultaneous Determination of Six Antiretroviral Drugs in Human Hair Using an LC-ESI+-MS/MS Method: Application to Adherence Assessment.

BACKGROUND
The determination of antiretroviral drugs in hair is receiving considerable research interest to assess long-term adherence to antiretroviral therapy (ART). Currently in China, lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir are combined as first- and second-line free therapy regimens and are recommended for people living with human immunodeficiency virus (HIV) (PLWH). Simultaneous determination of the six antiretroviral drugs in human hair is important for accurately and widely assessing long-term adherence in Chinese PLWH receiving different ART regimens.


METHODS
Six drugs were extracted from 10-mg hair samples incubated in methanol for 16 h at 37 °C and then analyzed by liquid chromatography with tandem mass spectrometry (LC-MS/MS) using a mobile phase of 95% methanol, with an electrospray ionization (ESI) source in multiple reaction monitoring and positive mode.


RESULTS
The LC-ESI+-MS/MS method exhibited a linear range (R2 > 0.99) within 6-5000, 10-5000, 6-50000, 12-50000, 8-5000, and 8-12500 pg/mg for lamivudine, zidovudine, nevirapine, efavirenz, ritonavir, and lopinavir. For all six drugs, the limits of quantification ranged between 6 and 12 pg/mg. The intra-day and inter-day coefficients of variation were within 15%, and the recoveries ranged from 91.1% to 113.7%. Furthermore, the other validation parameters (i.e., selectivity, matrix effect, stability, and carryover) met the acceptance criteria stipulated by guidelines of the United States Food and Drug Administration and European Medicines Agency. Significant intergroup differences were observed between high- and low-adherence groups, with high inter-correlations in the hair content of the six drugs.


CONCLUSIONS
The developed method demonstrated good reliability, to comprehensively and accurately assess adherence in PLWH receiving different ART regimens.