Development and Validation of a Bioanalytical Method for the Simultaneous Determination of 14 Antiretroviral Drugs using Liquid Chromatography-Tandem Mass Spectrometry

Daskapan, Alper; Hateren, Kai van; Stienstra, Ymkje; Kosterink, Jos G. W.; Werf, T. van der; Touw, Daan; Alffenaar, Jan-Willem

doi:10.17145/jab.18.007

Cited by 5 publications

(6 citation statements)

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“…This interpretation is based on metabolism studies [ 65 , 66 ]. The observation of the product ion with m/z 304 for the [D 8 ]-labelled analogue (with labels on the 4-cyano-2,6-dimethylphenyl moiety) [ 67 ] and for the [ 13 C 6 ]-labelled analogues (with labels at the phenyl ring in the 4-cyanophenyl moiety) [ 21 ] also supports part of the interpretation.…”

Section: Non-nucleoside Reverse Transcriptase Inhibitors (Nnrtis)mentioning

confidence: 79%

“…Because of the high inter- and intra-individual variability in the effectiveness of these drugs, therapeutic drug monitoring is required for these drugs. As a result, multi-analyte LC–MS methods for the bioanalysis PIs have been reported [ [12] , [13] , [14] , [17] , [18] , [19] , [20] , [21] , [22] , [23] , 54 , 70 ] and reviewed [ 6 , 7 ]. The protease inhibitors are generally analyzed in positive-ion mode.…”

Section: Protein Inhibitors (Pis)mentioning

confidence: 99%

“…An important issue in TDM is the frequent use of combination therapies in HIV treatment, wherein several antiviral agents are administered in combination [ 10 ]. To this end, the development and application of numerous multianalyte methods have been reported as well, involving the analysis of as many as 16 HIV-related antivirals [ [11] , [12] , [13] , [14] , [15] , [16] , [17] , [18] , [19] , [20] , [21] , [22] , [23] ]. In most cases, one (or more recently two) SRM transition have been used.…”

Section: Introductionmentioning

confidence: 99%

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Tandem mass spectrometry of small-molecule antiviral drugs: 1. HIV-related antivirals

Niessen¹

2020

International Journal of Mass Spectrometry

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Antiviral drugs are a class of compounds developed specifically for the treatment of viral infections. In the development and subsequent application of antiviral drugs, like for any other class of drugs, quantitative analysis in biological matrix is important, e.g., to establish bioavailability, to study pharmacokinetics, and later on possibly for therapeutic drug monitoring. Liquid chromatography–mass spectrometry (LC–MS) with tandem mass spectrometry (MS–MS) operated in selected-reaction monitoring (SRM) mode is the method of choice in quantitative bioanalysis. As information of the fragmentation of antiviral drugs in MS–MS is very much scattered in the scientific literature, it was decided to collect this information and to review it, not only to understand which product ions are actually used in SRM, but also to assist in other studies, e.g., in the identification of drug metabolites or (forced) degradation products. In this first study, attention is paid to antiviral agents used against HIV infection. The review provides fragmentation schemes of ca. 40 antiviral agents as well as several phosphorylated anabolites. The identity of the product ions used in SRM, i.e., elemental composition and exact- m/z , is tabulated, and more detailed fragmentation schemes are provided.

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Section: Non-nucleoside Reverse Transcriptase Inhibitors (Nnrtis)mentioning

confidence: 79%

Section: Protein Inhibitors (Pis)mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Tandem mass spectrometry of small-molecule antiviral drugs: 1. HIV-related antivirals

Niessen¹

2020

International Journal of Mass Spectrometry

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“…Darunavir plasma concentrations were analyzed by a validated liquid chromatography–tandem mass spectrometry method. 17…”

Section: Methodsmentioning

confidence: 99%

Darunavir Population Pharmacokinetic Model Based on HIV Outpatient Data

Daskapan

Tran

Cattaneo

et al. 2019

Therapeutic Drug Monitoring

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“…The importance of multianalyte bioanalytical methods [ 14 , 15 , 16 , 17 , 18 , 19 , 20 ] has been emphasized already in our above stated review papers. Various newly published research papers have also demonstrated successful use of LC-MS/MS methods for the simultaneous analysis of 7–16 antiviral agents [ 21 , 22 , 23 , 24 , 25 , 26 ]. Moreover, detailed MS/MS characterization of antivirals addressing selected reaction monitoring (SRM) data and also structure elucidation of individual fragments have been presented in extensive review articles for antivirals for HIV treatment [ 27 ], antivirals against hepatitis [ 28 ], and against herpes, influenza, and other viral infections [ 29 ].…”

Section: Introductionmentioning

confidence: 99%

Determination of Antiviral Drugs and Their Metabolites Using Micro-Solid Phase Extraction and UHPLC-MS/MS in Reversed-Phase and Hydrophilic Interaction Chromatography Modes

et al. 2021

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Two new ultra-high performance liquid chromatography (UHPLC) methods for analyzing 21 selected antivirals and their metabolites were optimized, including sample preparation step, LC separation conditions, and tandem mass spectrometry detection. Micro-solid phase extraction in pipette tips was used to extract antivirals from the biological material of Hanks balanced salt medium of pH 7.4 and 6.5. These media were used in experiments to evaluate the membrane transport of antiviral drugs. Challenging diversity of physicochemical properties was overcome using combined sorbent composed of C18 and ion exchange moiety, which finally allowed to cover the whole range of tested antivirals. For separation, reversed-phase (RP) chromatography and hydrophilic interaction liquid chromatography (HILIC), were optimized using extensive screening of stationary and mobile phase combinations. Optimized RP‑UHPLC separation was carried out using BEH Shield RP18 stationary phase and gradient elution with 25 mmol/L formic acid in acetonitrile and in water. HILIC separation was accomplished with a Cortecs HILIC column and gradient elution with 25 mmol/L ammonium formate pH 3 and acetonitrile. Tandem mass spectrometry (MS/MS) conditions were optimized in both chromatographic modes, but obtained results revealed only a little difference in parameters of capillary voltage and cone voltage. While RP-UHPLC-MS/MS exhibited superior separation selectivity, HILIC-UHPLC-MS/MS has shown substantially higher sensitivity of two orders of magnitude for many compounds. Method validation results indicated that HILIC mode was more suitable for multianalyte methods. Despite better separation selectivity achieved in RP-UHPLC-MS/MS, the matrix effects were noticed while using both chromatographic modes leading to signal enhancement in RP and signal suppression in HILIC.

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Development and Validation of a Bioanalytical Method for the Simultaneous Determination of 14 Antiretroviral Drugs using Liquid Chromatography-Tandem Mass Spectrometry

Cited by 5 publications

References 0 publications

Tandem mass spectrometry of small-molecule antiviral drugs: 1. HIV-related antivirals

Tandem mass spectrometry of small-molecule antiviral drugs: 1. HIV-related antivirals

Darunavir Population Pharmacokinetic Model Based on HIV Outpatient Data

Determination of Antiviral Drugs and Their Metabolites Using Micro-Solid Phase Extraction and UHPLC-MS/MS in Reversed-Phase and Hydrophilic Interaction Chromatography Modes

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