Improved methods for determining the concentration of 6-thioguanine nucleotides and 6-methylmercaptopurine nucleotides in blood

Pike, Michael; Franklin, Curtis L.; Mays, Dennis C.; Lipsky, James J.; Lowry, Philip W.; Sandborn, William J.

doi:10.1016/s0378-4347(00)00513-2

Cited by 37 publications

(59 citation statements)

References 17 publications

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“…The mean extraction efficiency was 87.8% for 6-MP, 90.9% for 6-TG and 92.1% for 6-MMP. Such recoveries are higher than that obtained by previous methods [1,[12][13][14][15][16][17], due to applying some modifications to the extraction process as advised by Hawwa et al [11]. Recovery seemed to increase with increasing drug concentrations, and performing a oneway ANOVA test revealed a statistically significant difference (p<0.05) between recovery % of low and high concentrations of the 3 analytes, however with no significant difference between the low/intermediate/ high concentrations.…”

Section: Recoverymentioning

confidence: 73%

“…LC-MS/MS and HPLC-UV are the two chromatographic techniques reported to measure 6-MP and its metabolites levels in blood [1,[11][12][13][14][15][16][17][18][19][20][21][22]. Each of the reported methods had its advantages and drawbacks, many of which were overcome by the present method, which measures 6-MP, 6-TG and 6-MMP by HPLC-UV in one sample using a single wavelength and a conventional C18 column.…”

Section: Introductionmentioning

confidence: 99%

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HPLC Determination of the Levels of 6-Mercaptopurine Metabolites Suitable for the Clinical Risk Assessment of its Toxicity among Egyptian Children with Acute Lymphocytic Leukemia

Abdelsayed¹,

A²,

Sidhom³

et al. 2017

J Anal Bioanal Tech

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The need of a robust, sensitive HPLC method for the quantitation of 6-thioguaninenucleotides (6-TG) and 6-methylmercaptopurine (6-MMP) is indispensable to relate levels of these metabolites with emergence of signs of toxicity in patients undergoing treatment with 6-mercaptopurine (6-MP), paving the road to accurate dose calculations and thus providing a cost-effective treatment approach. Previously reported methods were either laborious, required special types of C18 columns, or had long run times. A Design of Experiments (DoE) approach targeting the shortest run time with greatest selectivity was adopted using a user friendly HPLC method development simulation software (DryLab®). Analytes eluted within 10 min, at 3.8, 4.2, 5.6 and 7.5 min for 6-TG, 6-MP, 6-MMP and Dithiothreitol (DTT) respectively. Excellent recovery percentages of 90.9 ± 14.4, 87.8 ± 6.7 and 92.1 ± 9.08, respectively were obtained. The method proved its validity and robustness according to the International Conference on Harmonization (ICH) guidelines. The LOD of 6-MP, 6-TG and 6-MMP were 6, 9 and 24 pmol/8 × 108 RBCs, respectively. Twenty-Two Acute Lymphocytic Leukemia (ALL) children recruited from 57357 Cancer Hospital (Cairo, Egypt) had their 6-MP metabolites measured using the developed method. A strong negative correlation was manifested between TG and RBCs count and hemoglobin (p=0.009 and 0.002 respectively). WBC and neutrophils showed a negative correlation to TG at Continuation 1 phase of treatment, confirming the association of TG with myelotoxicity. The significant correlation between MMP and alanine aminotransferase (ALT) and aspartate aminotransferase (AST) (p=0.030, 0.004) explained its potential hepatotoxicity.

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Section: Recoverymentioning

confidence: 73%

Section: Introductionmentioning

confidence: 99%

HPLC Determination of the Levels of 6-Mercaptopurine Metabolites Suitable for the Clinical Risk Assessment of its Toxicity among Egyptian Children with Acute Lymphocytic Leukemia

Abdelsayed¹,

A²,

Sidhom³

et al. 2017

J Anal Bioanal Tech

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“…This solution was extracted with 1.0 mL dichloromethane and centrifuged for 10 min at 4000 rpm. 26 Aqueous supernatant (1.3 mL) was transferred into a clean 12 × 75 mm glass tube and aliquots of 0.1 mol L -1 sodium bicarbonate (pH 10.1) was added to adjust the solution pH to approximately 3.5. Then 30 µL of the supernatant was injected into the voltammetric cell.…”

Section: Preparation Of Real Samplesmentioning

confidence: 99%

“…Only three methods have been reported for the determination of thioguanine. [24][25][26] Those reported methods could not measure thioguanine less than 120 nmol L -1 . One of the important limitation of HPLC or spectrophotometric techniques is the fact that captopril and thioguanine lack sufficient UV absorption.…”

Section: Introductionmentioning

confidence: 99%

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Simultaneous determination of captopril and thioguanine in pharmaceutical compounds and blood using cathodic adsorptive stripping voltammetry

Ensafi¹,

Hajian²

2008

J. Braz. Chem. Soc.

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Apresentamos um procedimento altamente seletivo e sensível para a determinação simultânea de captopril e de tioguanina baseado em processo de redissolução catódica adsortiva dos complexos de Cu(I)-captopril e de Cu(I)-tioguanina em um eletrodo gotejante de mercúrio. Captopril e tioguanina foram pré-concentrados na superfície da gota do eletrodo de mercúrio usando Cu(II) como sensor e tempo de acumulação igual a 90 s. Em seguida, os complexos pré-concentrados foram analisados por voltametria adsortiva de pulso diferencial catódica. O efeito de vários parâmetros na sensibilidade, tais como, pH, concentração de cobre, potencial de acumulação, tempo de acumulação e velocidade de varredura, na sensibilidade do método foram estudados. As condições ótimas para a determinação simultânea de captopril e de tioguanina foram: pH = 3,5, concentração de cobre(II) = 45,0 ng mL -1 , potencial de acumulação = -0,10 V e velocidade de varredura = 60 mV s -1 . Nas condições ótimas e tempo de acumulação igual a 90 s, os picos de corrente medidos em torno de -0,15 V e -0,40 V (vs. Ag/AgCl) foram proporcionais às concentrações de tioguanina e de captopril nas faixas de 0,15-180 e 0,5-100 nmol L -1 . Os limites de detecção para tioguanina e captopril foram 0,08 e 0,3 nmol L -1 , respectivamente. Os desvios padrões relativos para cinco replicatas de 20,0 nmol L -1 de captopril e de tioguanina foram 2,5% e 2,1%. O método para a determinação de captopril e de tioguanina foi testado em amostras de misturas sintéticas, farmacêuticas e em soro humano, apresentando resultados satisfatórios.A reliable, highly selective and sensitive procedure is presented for simultaneous determination of captopril and thioguanine based on cathodic adsorptive stripping of Cu(I)-captopril and Cu(I)-thioguanine complexes on a hanging mercury drop electrode. Captopril and thioguanine were preconcentrated onto the surface of hanging mercury drop electrode using Cu(II) as a suitable probe, with accumulation time of 90 s. Then the preconcentrated complexes were analyzed by cathodic stripping differential pulse voltammetry. The effect of various parameters such as pH, concentration of copper, accumulation potential, accumulation time and scan rate on the sensitivity were studied. The optimum conditions for simultaneous determination of captopril and thioguanine include pH=3.5, 45.0 ng mL -1 copper(II) concentration, accumulation potential of -0.10 V and scan rate of 60 mV s -1 . Under the optimum conditions and for an accumulation time of 90 s, the measured peak currents at about -0.15 V and -0.40 V (vs. Ag/AgCl) are proportional to the concentrations of thioguanine and captopril over the ranges of 0.15-180 and 0.5-100 nmol L -1 , respectively. The limits of detection are 0.08 and 0.3 nmol L -1 for thioguanine and captopril, respectively. The relative standard deviations for five replicate analyses of 20.0 nmol L -1 captopril and thioguanine are 2.5% and 2.1%, respectively. The method was applied to the determination of captopril and thioguanine in synthetic mixed sa...

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Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases

el-Azhary¹,

Farmer²,

Drage³

et al. 2009

Arch Dermatol

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Improved methods for determining the concentration of 6-thioguanine nucleotides and 6-methylmercaptopurine nucleotides in blood

Cited by 37 publications

References 17 publications

HPLC Determination of the Levels of 6-Mercaptopurine Metabolites Suitable for the Clinical Risk Assessment of its Toxicity among Egyptian Children with Acute Lymphocytic Leukemia

HPLC Determination of the Levels of 6-Mercaptopurine Metabolites Suitable for the Clinical Risk Assessment of its Toxicity among Egyptian Children with Acute Lymphocytic Leukemia

Simultaneous determination of captopril and thioguanine in pharmaceutical compounds and blood using cathodic adsorptive stripping voltammetry

Thioguanine Nucleotides and Thiopurine Methyltransferase in Immunobullous Diseases

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