Development and validation of LC–MS/MS assay for the simultaneous determination of methotrexate, 6-mercaptopurine and its active metabolite 6-thioguanine in plasma of children with acute lymphoblastic leukemia: Correlation with genetic polymorphism

Al‐Ghobashy, Medhat A.; Hassan, Said A.; Abdelaziz, Doaa H.; Elhosseiny, Noha M.; Sabry, Nirmeen A.; Attia, Ahmed S.; El-Sayed, Manal Hamdy

doi:10.1016/j.jchromb.2016.10.035

Cited by 45 publications

(37 citation statements)

References 26 publications

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“…SPE procedure can be adjusted to improve the procedure efficiency, such as the sorbent choice, adequate solvents for conditioning and washing of the cartridges and the analyte elution (Thurman, ). Different sorbents have been used for extraction of MTX and its metabolites, such as phenyl (Begas et al, ), Oasis MAX (Hawwa et al, ) and Oasis HLB cartridges (van Haandel et al, ) and Bondesil SCX (Al‐Ghobashy et al, ). Various protocols have been published depending on the sorbent used.…”

Section: Liquid Chromatographymentioning

confidence: 99%

“…Elimination of the interferences was achieved by washing the cartridges with organic solvents, acid or alkaline aqueous solutions (Al‐Ghobashy et al, ; Begas et al, ;Hawwa et al, ; van Haandel et al, ). Analytes were eluted from the cartridges with organic solvents or a mixture of organic solvents with acid or alkaline aqueous solutions, depending on the sorbent used (Al‐Ghobashy et al, ; Begas et al, ; Hawwa et al, ; van Haandel et al, ). Finally, the eluent was evaporated to dryness and the residue reconstituted in a suitable volume of solvent for injection into the chromatographic system.…”

Section: Liquid Chromatographymentioning

confidence: 99%

“…Mean recovery of MTX was 93.1–98.2%. using phenyl cartridges (Begas et al, ) and 94.3% using Bonsedil SCX cartridges (Al‐Ghobashy et al, ). Recoveries for MTX and MTXPGs ranged from 44 to 70% using Oasis MAX cartridges, and for MTXPGs it ranged from 31 to 51% using Oasis HLB cartridges (Hawwa et al, ; van Haandel et al, ).…”

Section: Liquid Chromatographymentioning

confidence: 99%

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Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

Silva

Ribeiro

Gonçalves

et al. 2018

Biomedical Chromatography

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Methotrexate (MTX) is an antifolate drug used for several diseases. Depending on the disease, MTX can be administered at low dose (LDMTX) in some autoimmune diseases, like rheumatoid arthritis, or at high dose (HDMTX) in some cancers, such as acute lymphoblastic leukemia. After absorption, MTX is metabolized in the liver to 7-hydroxymethotrexate and in the intestine to 2,4-diamino-N10-methylpteroic acid (DAMPA). Moreover, inside red blood cells, MTX is converted to active metabolites, MTX polyglutamates (MTXPGs), contributing to its pharmacodynamics. Owing to its narrow therapeutic range, and inter- and intra-patient variability, either noneffectiveness and/or toxicity may occur. Because of the existence of a relationship between drug therapeutic outcome and its systemic concentration, therapeutic drug monitoring (TDM) may ensure the effectiveness and safety of MTX use. In order to monitor the optimization of patient clinical response profile, several analytical methods have been described for TDM in biological samples. These include liquid chromatography (LC) coupled with ultraviolet detection, fluorescence detection or mass spectrometry, each one presenting advantages and drawbacks. This paper reviews the most commonly used techniques for sample preparation and critically discusses the current LC methods applied for the TDM of MTX in biological samples, at LDMTX and HDMTX.

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Section: Liquid Chromatographymentioning

confidence: 99%

Section: Liquid Chromatographymentioning

confidence: 99%

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Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

Silva

Ribeiro

Gonçalves

et al. 2018

Biomedical Chromatography

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“…The final 6-MP pathway involves methylation to 6-methylmercaptopurine (6-MMP) by thiopurine methyltransferase (TPMT) [6]. High concentrations of 6-TG have been found to correlate with therapeutic efficacy, and high 6-MMP concentrations were associated with liver toxicity [7]. Since the metabolite formation of 6-MP is affected by TPMT enzymes that undergo polymorphism, the effects of 6-MP treatment vary widely among individuals.…”

Section: Introductionmentioning

confidence: 99%

“…Several analysis methods of 6-MP and 6-TG in whole blood or plasma have been done before; ultra-high-performance liquid chromatographytandem mass spectrometry (UPLC-MS/MS) had been used to analyze both 6-MP and 6-TG in plasma samples [7] and 6-MP metabolites in whole blood samples [10]. On the other hand, a method for analysis of dry blood is still not available.…”

Section: Introductionmentioning

confidence: 99%

Validation of 6-Mercaptopurine and 6-Thioguanine in Dried Blood Spot by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

2018

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Objective: This study aimed to obtain an optimal and validated method of analyzing 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) simultaneously in dried blood spot samples using ultra high-performance liquid chromatography-tandem mass spectrometry. Method:Separation was performed with a 1.7-μm amide column, which had a mobile phase with a flow rate of 0.2 mL/min and comprised 0.2% formic acid in water, 0.1% formic acid in acetonitrile, and methanol with a gradient elution. Detection was performed using Waters Xevo TQD.Result: This method was linear with a range of 25-1000 ng/mL for 6-MP and 6-TG, with consecutive r values of ≥0.996 and ≥0.995, respectively. The intra-and inter-day % difference value and coefficient of variation for the accuracy and precision were not more than 15% and 20%, respectively, at a concentration lower limit of quantitation. Conclusion:This method fulfilled the requirements of the European Medicines Agency guideline for validation.

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Development and validation of stability indicating reversed‐phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation

Pandey

Mahtab

Singh

et al. 2018

Biomedical Chromatography

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Methotrexate (MTX) and teriflunomide (TEF) are the two most effective disease-modifying antirheumatic drugs used as combination therapy for rheumatoid arthritis and no robust high-performance liquid chromatography (HPLC) method is available for their simultaneous estimation to date. Therefore, we have developed and validated an isocratic reversed-phase HPLC method for simultaneous analysis of MTX and TEF spiked in the form of active pharmaceutical ingredients, tablets and nanoformulations. The best separation was achieved on a BDS, C , 4.6 × 250 mm, 5 μm analytical column (Thermo Hypersil) with methanol-ethylammonium formate-potassium dihydrogen phosphate buffer (55 mm, pH 3.5; 65:5:30, v/v) as mobile phase at a flow rate of 0.8 mL/min. All the samples were subjected to force degradation studies. Responses of MTX and TEF were found to be a linear function of concentration over the range 1-50 μg/mL (r = 0.9976 and 0.9982). The limits of detection and limit of quantification were 7.74 and 25.82 ng/mL and 10.74 and 35.80 ng/mL, respectively. Degradation products produced under the stress studies did not interfere with the detection of MTX and TEF and therefore the developed method can be regarded as stability indicating.

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Development and validation of LC–MS/MS assay for the simultaneous determination of methotrexate, 6-mercaptopurine and its active metabolite 6-thioguanine in plasma of children with acute lymphoblastic leukemia: Correlation with genetic polymorphism

Cited by 45 publications

References 26 publications

Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

Liquid chromatographic methods for the therapeutic drug monitoring of methotrexate as clinical decision support for personalized medicine: A brief review

Validation of 6-Mercaptopurine and 6-Thioguanine in Dried Blood Spot by Ultra Performance Liquid Chromatography-Tandem Mass Spectrometry

Development and validation of stability indicating reversed‐phase liquid chromatographic method for simultaneous quantification of methotrexate and teriflunomide in nanoparticles and marketed formulation

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