Determination of hydroxyurea in plasma and peritoneal fluid by high-performance liquid chromatography using electrochemical detection

Pujari, Mahesh P.; Barrientos, Alfonso; Muggia, Franco M.; Koda, Robert T.

doi:10.1016/s0378-4347(97)00120-5

Cited by 22 publications

(11 citation statements)

References 7 publications

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“…A C 18 analytical column was purchased from BioRad (Richmond, Calif., USA). Each plasma and urine sample was filtered through a Nalgene disposable (0.2-Ìm pore size) filter (Nalgene, Rochester, N.Y., USA) that was attached to a 1.0-ml syringe (Becton Dickinson, Rutherford, N.J., USA).…”

Section: Apparatus and Chromatographic Conditionsmentioning

confidence: 99%

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Pharmacokinetic Profile of the Anti-Sickling Hydroxyurea in Wild-Type and Transgenic Sickle Cell Mice

2001

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The pharmacokinetic profile of hydroxyurea (HU) was investigated by measuring the rate of drug disappearance from the plasma in wild-type and transgenic (Tg) sickle cell mice. The absorption and elimination processes of HU exhibited first-order kinetics after intraperitoneal administration of HU at 10, 50, 100 or 200 mg/kg body weight (BW). The dosage had a marked effect on the pharmacokinetics of HU in the Tg sickle cell mice. Although the area under the plasma concentration curve (AUC) increased in direct proportion with the HU dose in the wild-type mice, the AUC increased to a much greater extent at higher doses in the Tg sickle cell mice. In the Tg sickle cell mice, there was a considerable increase in the mean residence time (MRT) and a significant reduction in the apparent clearance (CL/F) at HU dose ≧100 mg/kg BW, when compared to the lower doses. At an HU dose of 200 mg/kg BW, the CL/F in the Tg sickle cell mice was reduced by about 50% of the value obtained at a dose of 10 mg/kg BW. This phenomenon was not noticeable in the wild-type mice. The MRT value in the wild-type mice at all doses was relatively constant. The steady-state distribution volume of HU in both the wild-type and Tg sickle cell mice was relatively constant at all doses of the drug. The AUC, CL/F, MRT, and terminal half-life values at any given HU dose showed significant differences between the wild-type and Tg sickle cell mice. Following intraperitoneal administration of HU at a dose of 10, 50, 100, or 200 mg/kg BW, the mean percentage of HU excreted in the urine of the wild-type and Tg sickle cell mice over 120 min was 84 ± 6.4% and 50 ± 8.2%, respectively, indicating a significant difference in the amount of HU excreted in urine in the two kinds of mice. The results obtained in this study may be useful in establishing an optimal dose of HU in the treatment and management of patients with sickle cell disease and other hemoglobinopathies.

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Section: Apparatus and Chromatographic Conditionsmentioning

confidence: 99%

“…The highly sensitive and specific assay is a modification of the method reported by Pujari et al [18]. A stock solution of HU was prepared by dissolving 15 mg HU in 10 ml saline.…”

Section: Hydroxyurea Assaymentioning

confidence: 99%

Pharmacokinetic Profile of the Anti-Sickling Hydroxyurea in Wild-Type and Transgenic Sickle Cell Mice

2001

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“…Hydroxyurea was determined to have a retention time of 7.9 min and methylurea, the internal standard, 17.2 min. A more sensitive method was developed by Pujari et al [21] to measure hydroxyurea in human plasma and peritoneal fluid. The authors used HPLC in conjunction with electrochemical detection.…”

Section: Introductionmentioning

confidence: 99%

Quantitative analysis of trimethylsilyl derivative of hydroxyurea in plasma by gas chromatography–mass spectrometry

James

Nahavandi

Wyche

et al. 2006

Journal of Chromatography B

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“…The first one was described by Pujari and collaborators [16] and was composed of 0.2 M perchlorate and methanol 95/5 (V/V) (Sigma Aldrich, Steinheim, Germany). The…”

Section: Chemicals and Pre-analytical Treatmentmentioning

confidence: 99%

Development and Validation of a Liquid Chromatography Method with Electrochemical Detection for Hydroxyurea Quantification in Human Plasma and Aqueous Solutions

Rodríguez¹,

Beukens²,

Debouge

et al. 2014

J Chromatogr Sep Tech

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Hydroxyurea is the unique drug having demonstrated a significant efficacy in sickle cell disease treatment. We developed a liquid chromatography method with electrochemical detection for hydroxyurea analysis in plasma and aqueous solutions. Analytical goals included an analytical range from 2 to 50 mg/L, a total imprecision lower than 15% and a total error lower than 30%. After protein precipitation with acetonitrile, the separation was performed on a C18 Atlantis T3 column and eluted with sodium acetate 25 mM, acetonitrile 2.5%, pH 6.5. Thioacetamide was used as internal standard. The method was linear for drug concentrations ranging from 0.5 to 50 mg/L and recovery was comprised between 100 and 120%. The intra-day precision was lower than 6.0% and between-day precision was lower than 11%. The detection limit was 0.18 and 0.63 mg/L for aqueous solution and plasma, respectively and the quantification limit was 1.0 and 1.2 mg/L for aqueous solution and plasma, respectively. No interference from urea was observed. The liquid chromatography method developed can be used for pharmacokinetic studies in plasma and other biological samples such as saliva or urine. It requires low sample volumes and a simple pre-treatment and it allows a direct measure of non-derivatized hydroxyurea.

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Determination of hydroxyurea in plasma and peritoneal fluid by high-performance liquid chromatography using electrochemical detection

Cited by 22 publications

References 7 publications

Pharmacokinetic Profile of the Anti-Sickling Hydroxyurea in Wild-Type and Transgenic Sickle Cell Mice

Pharmacokinetic Profile of the Anti-Sickling Hydroxyurea in Wild-Type and Transgenic Sickle Cell Mice

Quantitative analysis of trimethylsilyl derivative of hydroxyurea in plasma by gas chromatography–mass spectrometry

Development and Validation of a Liquid Chromatography Method with Electrochemical Detection for Hydroxyurea Quantification in Human Plasma and Aqueous Solutions

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