Determination of Concentrations of Azathioprine Metabolites 6-Thioguanine and 6-Methylmercaptopurine in Whole Blood With the Use of Liquid Chromatography Combined With Mass Spectrometry

Żochowska, Dorota; Żegarska, Jolanta; Hryniewiecka, Ewa; Samborowska, Emilia; Jaźwiec, Radosław; Tszyrsznic, W.; Borowiec, Agnieszka; Dadlez, Michał; Pączek, Leszek

doi:10.1016/j.transproceed.2016.01.084

Cited by 18 publications

(17 citation statements)

References 13 publications

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“…6-Thioguanine (6TG) is an example of antimetabolite of natural purine bases whose action mechanism consists mainly in incorporation of the DNA and RNA chains in the form of nucleosides and blocking purine de novo biosynthesis. 6TG can act as an antiangiogenous molecule which is of significant importance in antitumorous therapy (Zochowska et al 2016).…”

Section: Introductionmentioning

confidence: 99%

Influence of nonionic surfactants and water activity on to adsorption of 6-thioguanine at the mercury/chlorates(VII) interface

et al. 2018

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The mixed adsorption layers of 6-thioguanine-TritonX-100 and 6-thioguanine-Tween 80 formed at the electrode/chlorate(VII) interface are discussed. The systems were characterized by measurements of differential capacity, zero charge potential, and surface tension at this potential. It was found that 6-thioguanine dominates in the formation of adsorption equilibria of the studied mixture. Competitive adsorption between 6-thioguanine-Triton X-100 and 6-thioguanine-Tween 80, ClO ions or mixed micelles cannot be excluded.

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Section: Introductionmentioning

confidence: 99%

Influence of nonionic surfactants and water activity on to adsorption of 6-thioguanine at the mercury/chlorates(VII) interface

et al. 2018

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“…On this topic, 5 studies [ 34 , 36 , 48 , 81 , 108 ] evaluated the relation between 6-TGN levels and hemoglobin and registered a significant but weak weighted mean correlation ( Figure 2 a). When the analysis was restricted to studies with IBD patients [ 34 , 36 , 48 ], the strength of the correlation improved (r = −0.28, 95% CI −0.50; −0.06; p = 0.01) ( Figure S4 ).…”

Section: Resultsmentioning

confidence: 99%

Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

Sousa

Estevinho

Dias

et al. 2020

JCM

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Many questions remain unanswered regarding therapeutic drug monitoring (TDM) utility with thiopurines. This study aims to establish a relationship between thiopurines’ metabolites and drug toxicity. We performed a systematic review with inclusion of studies evaluating the relationship between thiopurines’ metabolites and drug toxicity. Meta-analysis of mean difference (MD), correlations and odds ratio (OR) was performed. We identified 21,240 records, 72 of which were eligible for meta-analysis. Levels of 6-thioguanine nucleotides (6-TGN) were higher in patients with leukopenia (MD 127.06 pmol/8 × 108 RBC) and gastrointestinal intolerance (MD 201.46 pmol/8 × 108 RBC), and lower in patients with hepatotoxicity (MD −40.6 pmol × 108 RBC). We established a significant correlation between 6-TGN and leukocytes (r = −0.21), neutrophils (r = −0.24) and alanine aminotransferase levels (r = −0.24). OR for leukopenia in patients with elevated 6-TGN was 4.63 (95%CI 2.24; 9.57). An optimal cut-off of 135 pmol/8 × 108 RBC for leukopenia was calculated (sensitivity 75.4%; specificity 46.4%). 6-methylmercaptopurine ribonucleotides (6-MMPR) were significantly associated with hepatotoxicity (MD 3241.2 pmol/8 × 108 RBC; OR 4.28; 95%CI 3.20; 5.71). Levels of 6-MMPR measured in the first 8 weeks of treatment were associated with leukopenia. We conclude that TDM could be used to prevent thiopurines’ toxicity. As optimal metabolites level may vary according to indication, physicians may adapt posology to decrease toxicity without compromising efficacy.

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“…120,121,125 6-Methylmercaptopurine produced by TPMT was frequently sought in globules of patients undergoing treatment to define their phenotyping, since TPMT deficiency led to severe toxicity. 121 In addition to UV detection (which was the most widely used), amperometric detection (AD), 129 fluorescence detection (FD) 130 and MS detection 121,126,127,131 were also coupled to LC for the determination of purine analogues. LOQ of 1 ng mL −1 were usually obtained for purine analogues determination by LC-MS. 127,126 Concentrations of 6-mercaptopurine at 0.0615 ng mL −1 in urine samples were detected by a LC-FD method using metal palladium to form coordination complexes and enhance the detection signal.…”

Section: Analyst Critical Reviewmentioning

confidence: 99%

Antineoplastic drugs and their analysis: a state of the art review

Guichard

Guillarme

Bonnabry

et al. 2017

Analyst

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The number of patients suffering from cancer is constantly increasing and, consequently, the number of different chemotherapy treatments administered is increasing. Given the high reactivity and toxicity of antineoplastic drugs, analytical methods are required in all pharmaceutical fields, from drug development to their elimination in wastewater; including formulation quality control, environment and human exposure and therapeutic drug monitoring. The aim of this paper is to provide an overview of the analytical methods available for the determination of antineoplastic drugs in different matrices such as pharmaceutical formulations, biological and environmental samples. The applicability and performance of the reported methods will be critically discussed, with focus on the most commonly used antineoplastic drugs. Only conventional compounds and small molecules for targeted therapy will be considered in the present review.

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Determination of Concentrations of Azathioprine Metabolites 6-Thioguanine and 6-Methylmercaptopurine in Whole Blood With the Use of Liquid Chromatography Combined With Mass Spectrometry

Cited by 18 publications

References 13 publications

Influence of nonionic surfactants and water activity on to adsorption of 6-thioguanine at the mercury/chlorates(VII) interface

Influence of nonionic surfactants and water activity on to adsorption of 6-thioguanine at the mercury/chlorates(VII) interface

Thiopurines’ Metabolites and Drug Toxicity: A Meta-Analysis

Antineoplastic drugs and their analysis: a state of the art review

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