Elsevier

Talanta

Volume 224, 1 March 2021, 121862
Talanta

Review
Detection and quantification of Covid-19 antiviral drugs in biological fluids and tissues

https://doi.org/10.1016/j.talanta.2020.121862Get rights and content

Highlights

  • Fourteen antiviral drugs were tested to counteract the effects of COVID-19.

  • A review of analytical methods for antivirals detection is presented.

  • Method validation, drugs extraction, separation and detection are discussed.

  • LC-MS and MS/MS is mostly used for accurate and sensitive drugs quantification.

Abstract

Since coronavirus disease 2019 (COVID-19) started as a fast-spreading pandemic, causing a huge number of deaths worldwide, several therapeutic options have been tested to counteract or reduce the clinical symptoms of patients infected with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Currently, no specific drugs for COVID-19 are available, but many antiviral agents have been authorised by several national agencies. Most of them are under investigation in both preclinical and clinical trials; however, pharmacokinetic and metabolism studies are needed to identify the most suitable dose to achieve the desired effect on SARS-CoV-2. Therefore, the efforts of the scientific community have focused on the screening of therapies able to counteract the most severe effects of the infection, as well as on the search of sensitive and selective analytical methods for drug detection in biological matrices, both fluids and tissues. In the last decade, many analytical methods have been proposed for the detection and quantification of antiviral compounds currently being tested for COVID-19 treatment. In this review, a critical discussion on the overall analytical procedure is provided, i.e (a) sample pre-treatment and extraction methods such as protein precipitation (PP), solid-phase extraction (SPE), liquid–liquid extraction (LLE), ultrasound-assisted extraction (UAE) and QuEChERS (quick, easy, cheap, effective, rugged and safe), (b) detection and quantification methods such as potentiometry, spectrofluorimetry and mass spectrometry (MS) as well as (c) methods including a preliminary separation step, such as high performance liquid chromatography (HPLC) and capillary electrophoresis (CE) coupled to UV–Vis or MS detection. Further current trends, advantages and disadvantages and prospects of these methods have been discussed, to help the analytical advances in reducing the harm caused by the SARS-CoV-2 virus.

Keywords

SARS-CoV-2
Antivirals
Analytical methods
Biological matrices
Mass spectrometry
Liquid chromatography

Abbreviations

ACN
acetonitrile
AD
absolute deviation
ADME
adsorption, distribution, metabolism, and elimination
BeWos
human placental choriocarcinoma trophobplast cells
CE
capillary electrophoresis
CHCA
α-cyano-4-hydroxycinnamic acid
CRMs
certified reference materials
CSF
cerebrospinal fluid
CV
coefficient of variation
DEV
deviation from nominal concentration value
DHB
2,5-dihydroxybenzoic acid
d-SPE
dispersive-sold-phase extraction
EMA
European Medicines Agency
Err
absolute value of the relative error
ESI
electrospray ionization
FDA
Food and Drug Administration
FL
fluorescence
HILIC
hydrophilic interaction liquid chromatography
HLB
hydrophilic-lipophilic balance
ICH
International Conference on Harmonization
LC
liquid chromatography
LLE
liquid-liquid extraction
LOD
limit of detection
LLOQ
lower limit of quantification
LOQ
limit of quantification
MALDI
matrix-assisted laser desorption/ionization
MCX
mixed-mode cationic exchange
MLC
micellar liquid chromatography
MRM
Muliple Reaction Monitoring
MSI
MALDI-MS Imaging
MTBE
methyltertbutyl ether
MS
mass spectrometry
NRTIs
nucleoside reverse transcriptase inhibitors
OSP
oseltamivir phosphate
PBA
phenylboronic acid
PBMCs
peripheral blood mononuclear cells
Ph. Eur
European Pharmacopoeia
PIs
protease inhibitors
PMA
phosphomolybdic acid
PP
protein precipitation
PSA
primary-secondary amine
Q
QuEChERS
QC
quality control
Q-MSI
quantitative MALDI-MS Imaging
RdRpIs
RNA polymerase inhibitors
RE
relative error
RSD
relative standard deviation
SDS
sodium dodecyl sulfate
SPE
solid-phase extraction
SRM
Selected Reaction Monitoring
TDM
therapeutic drug monitoring
TCA
trichloroacetic acid
UAE
ultrasound assisted extraction
UHPLC
ultra-high performance liquid chromatography

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