Detection of allopurinol and oxypurinol in canine urine by HPLC/MS-MS: Focus on veterinary clinical pharmacokinetics

Godoy, A.J.; Jesus, Clauceane de; Gonçalves, Rafaela Silva Guimarães; Azeredo, Francine Johansson; Rocha, Adriana; Marques, Maria Paula; Lanchote, Vera Lúcia; Larangeira, Daniela Farias; Barrouin‐Melo, Stella Maria

doi:10.1016/j.jpba.2020.113204

Cited by 3 publications

(11 citation statements)

References 25 publications

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“…Furthermore, other studies also showed the use of acyclovir as IS did not compromise the accuracy, precision of obtained concentrations and the reliability of the allopurinol bioanalytical methods. 3,12 Two common plasma sample preparation used for the quantification of allopurinol in biological matrix were liquid-liquid extraction (LLE) 3,8,11 and protein precipitation (PPT) techniques. [4][5][6][7]9,10,12 When liquid-liquid extraction (LLE) method was applied in the sample preparation of human plasma for bioequivalence studies of allopurinol, 3,8 the recovery (extraction efficiency) value of ≤ 65% was unsatisfactory.…”

Section: Methods Developmentmentioning

confidence: 99%

“…3,12 Two common plasma sample preparation used for the quantification of allopurinol in biological matrix were liquid-liquid extraction (LLE) 3,8,11 and protein precipitation (PPT) techniques. [4][5][6][7]9,10,12 When liquid-liquid extraction (LLE) method was applied in the sample preparation of human plasma for bioequivalence studies of allopurinol, 3,8 the recovery (extraction efficiency) value of ≤ 65% was unsatisfactory. 3,8,14 LLE method was not suitable for polar compound due to strong binding between polar compound and the plasma proteins, which could impede complete drug removal by organic solvents.…”

Section: Methods Developmentmentioning

confidence: 99%

“…The validated bioanalytical method was subsequently applied to the analysis of plasma samples after the oral administration of a single dose of 300 mg of allopurinol tablet (Zyloric tablet, Aspen Port Elizabeth (Pty) Ltd, South Africa) on twelve (12) healthy adult male subjects (18-55 years old, BMI between 18.0-30.0 kg/m 2 ) under fasting condition. The study was approved by Malaysia Medical Research and Ethics Committee and conducted in accordance with regulatory guidelines.…”

Section: Pharmacokinetic Study and Incurred Sample Reanalysis (Isr)mentioning

confidence: 99%

“…The improvement in the recovery of allopurinol when a mixture of acetone-acetonitrile (50: 50, v/v) was used as protein precipitation agent, as compared to previous studies where acetonitrile alone was used as protein precipitation agent is attributed to the relatively higher solubility in acetone than acetonitrile. 7,10,12 Zheng et al 35 studied the solubility of allopurinol in 15 neat solvents and reported the solubility of allopurinol was in the descending order of acetone, followed by acetonitrile and methanol.…”

Section: Recoverymentioning

confidence: 99%

“…Bioanalytical methods using HPLC-UV and LC-MS/ MS for the quantification of allopurinol in human serum, 3 human plasma, [4][5][6][7][8][9][10] rat plasma, 11 human urine 5,8 and canine urine 12 have been reported. Nevertheless, bioanalytical methods using HPLC-UV showed various limitations, such as injection of large sample volume of ≥ 20 µL to achieve sufficient sensitivity and relatively long sample elution time with retention time of allopurinol more than 6 min.…”

Section: Introductionmentioning

confidence: 99%

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Sample preparation and quantification of polar drug, allopurinol, in human plasma using LCMSMS

Wong

Loh

Goh

et al. 2022

Eur J Mass Spectrom (Chichester)

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A fast, selective and reproducible LC-MS/MS method with simple sample preparation was developed and validated for a polar compound, allopurinol in human plasma, using acyclovir as internal standard (IS). Chromatographic separation was achieved using Agilent Poroshell 120 EC-C18 (100 × 2.1 mmID, 2.7 µm) analytical column. The mobile phase was comprised of 0.1%v/v formic acid-methanol (95:05; v/v), at a flow rate of 0.45 mL/min. The effect of different protein precipitation agents used in sample preparation such as methanol, acetonitrile, a mixture of acetonitrile-methanol and a mixture of acetonitrile-acetone were evaluated to optimize the extraction efficiency of allopurinol and IS. The use of acetone-acetonitrile (50:50, v/v) as protein precipitating agent shortened the sample preparation time and improved the recovery of allopurinol to above 93%. The IS-normalised matrix factors at two concentration levels were 1.0, with CV of 5.1% and 4.2%. Allopurinol in plasma was stable at benchtop for 24 h, in autosampler tray for 48 h, in instrumentation room for 48 h, in freezer after 7 freeze-thaw cycles and in freezer for 140 days. Allopurinol stock standard solutions were stable for 140 days at room temperature and in the chiller. The short sample run time of the validated bioanalytical method allowed high throughput analysis of plasma samples in pharmacokinetic study of an allopurinol formulation. The robustness and reproducibility of the bioanalytical method was reaffirmed through incurred sample reanalysis (ISR).

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Section: Methods Developmentmentioning

confidence: 99%

Section: Methods Developmentmentioning

confidence: 99%

Section: Pharmacokinetic Study and Incurred Sample Reanalysis (Isr)mentioning

confidence: 99%

Section: Recoverymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Sample preparation and quantification of polar drug, allopurinol, in human plasma using LCMSMS

Wong

Loh

Goh

et al. 2022

Eur J Mass Spectrom (Chichester)

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The integrated analysis strategy of unstable hypoxanthine, a potential quality marker in Shuxuetong injection based on standard addition method and multi-level pharmacokinetics by LC-MS/MS

Xing

Wang

et al. 2023

Acupuncture and Herbal Medicine

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Objective: As an injection made from traditional Chinese medicine, Shuxuetong (SXT) injection is used for the treatment of ischemic stroke. Hypoxanthine is regarded as one of its potential quality markers. The purpose of this study is to lay the foundation for the quality control of SXT injection by the analysis of the quantitation and pharmacokinetic behavior of hypoxanthine. Methods: A quantitative method of hypoxanthine in SXT injection based on standard addition method by liquid chromatography-tandem mass spectrometry (LC-MS/MS) was established for the first time. On the other hand, a determination method of hypoxanthine in rat plasma samples after administration of SXT was also successfully established based on LC-MS/MS. Results: It was found that the content of hypoxanthine was higher using conventional liquid-mass spectrometry technology compared to the application of LC-MS/MS combined standard addition method in the same batch of SXT injection. The ratio of low, medium and high doses of intravenous SXT were 1:2:4, and the AUC0-t was (848.34 ± 324.53) μg·h/L, (1483.94 ± 497.74) μg·h/L, and (3074.84 ± 910.29) μg·h/L, respectively. AUC0-t shows a good linear dose-dependent relationship. Conclusions: The influences of endogenous substances tend to be eliminated by calibrating the concentration level of the target compound by the introduction of the standard addition method. The added allopurinol could inhibit the conversion of the target compound, and ensure the accuracy of the detection during the pharmacokinetic studies. “Blank biological matrix” obtained from the pretreatment of blank plasma successfully distinguished endogenous and drug-derived hypoxanthine. There is a good linear relationship between the blood concentration of intravenous hypoxanthine and the dosage of administration. Similarly, there was no drug accumulation in the multiple medium-dosage group, which is similar to the pharmacokinetic characteristics of the single medium-dosage group. Graphical abstract: http://links.lww.com/AHM/A59

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High Performance Liquid Chromatography Analysis and Description of Purine Content of Diets Suitable for Dogs with Leishmania Infection during Allopurinol Treatment—A Pilot Trial

Kaempfle,

Bergmann,

Koelle

et al. 2023

Animals

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Reducing the alimentary purine intake contributes to the prevention of purine (especially xanthine) urolith formation, a common adverse effect of allopurinol treatment in dogs with Leishmania infections. Analyses of the purine content are not required in order to advertise a diet as low in purine. Due to different analytical methods, data provided on purine content are barely comparable. The aim of this study was to investigate the total purine content of 12 different dog diets. For this, the purine bases adenine, guanine, xanthine, and hypoxanthine were determined by standardised high performance liquid chromatography in commercially available urinary diets (n = 4), kidney diets (n = 2), low protein diets (n = 3), 1 vegan diet, 1 regular diet for healthy adult dogs, and 1 homemade low purine diet. Total purine amounts ranged between 10.2 and 90.9 mg/100 g of dry matter. The daily purine intake calculated for a 20 kg standard dog with the analysed diets ranged between 21.9 and 174.7 mg. The lowest daily purine intakes were achieved by 2 urinary urate diets, followed by the homemade diet. Differences in the purine content of commercially available diets need to be considered. Awareness has to be raised when selecting diets for dogs with Leishmania infections during allopurinol treatment in order to minimise the risk of urolith formation.

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Detection of allopurinol and oxypurinol in canine urine by HPLC/MS-MS: Focus on veterinary clinical pharmacokinetics

Cited by 3 publications

References 25 publications

Sample preparation and quantification of polar drug, allopurinol, in human plasma using LCMSMS

Sample preparation and quantification of polar drug, allopurinol, in human plasma using LCMSMS

The integrated analysis strategy of unstable hypoxanthine, a potential quality marker in Shuxuetong injection based on standard addition method and multi-level pharmacokinetics by LC-MS/MS

High Performance Liquid Chromatography Analysis and Description of Purine Content of Diets Suitable for Dogs with Leishmania Infection during Allopurinol Treatment—A Pilot Trial

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