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A rapid and sensitive High-Performance Liquid Chromatography-tandem Mass Spectrometry method for determining apremilast in beagle dog plasma and urine: Application in a pharmacokinetic study

100%

Yan G. , Yu L. , Chen X. , Tran T. , Nguyen L. , Zhijun W. , Wang L.

Acta Chromatographica

2021

tom Vol. 33, no. 2

112--119

A rapid and sensitive High-Performance Liquid Chromatography-tandem Mass Spectrometry (HPLC/MS/MS) method for determining apremilast in beagle dog plasma and urine samples was developed and validated using clopidogrel as the internal standard (IS). Apremilast was extracted from the plasma and urine samples by liquid–liquid extraction using methyl tert-butyl ether. Chromatographic separation was performed using a C8 column with gradient elution and a mobile phase containing methanol and 0.1% formic acid. Quantification was achieved in multiple reaction monitoring (MRM) mode with a transition of m/z 461.3→178.2 for apremilast and m/z 322.2→184.1 for clopidogrel (IS). This method was validated regarding its specificity, linearity, precision, accuracy, and stability. The lower limit of quantification (LLOQ) for this method was 5 ng/mL, and the calibration curve was linear over 5–1,000 ng/mL. The intra- and inter-run coefficients of variance (CV) of aprelimast in plasma samples were less than 12.92% and 10.64%, respectively, while in urine samples, the CV were less than 11.84% and 10.20%, respectively. The samples were stable under the tested conditions. This method was successfully applied to a pharmacokinetic study in beagle dogs following oral administration of 10 mg of apremilast.

Renal haemodynamics and natriuretic responses to intravenous administration of diadenosine tetraphosphate [AP4A] and nicotinamide adenine dinucleotide [NAD] in rat

75%

Szczepanska-Konkel M. , Langner G. , Bednarczuk G. , Stiepanow-Trzeciak A. , Jankowski M. , Angielski S.

Journal of Physiology and Pharmacology

2003

tom 54

nr 2

Effects of Ap4A and NAD - precursor of adenosine, on renal plasma flow (RPF), glomerular filtration rate (GFR) and urine excretion were determined in the anaesthetised rats. Infusion of Ap4A or NAD (i.v., bolus - 1 µmol/kg followed by 10 nmol/min/kg) decreased RPF and GFR (by 30 and 40%, respectively). In spite of GFR reduction during Ap4A infusion, the significant increase in sodium excretion and urine flow was noticed: fractional sodium (FENa) and urine excretion (FEurine) rose 15-fold and 2.5-fold in comparision with the control value, respectively. In contrast to Ap4A, NAD-induced decrease in GFR was associated with parallel decrease in sodium and urine excretion, thus the FENa and FEurine did not significantly change. Pre-treatment with adenosine deaminase (adenosine degrading enzyme, 2 U/min/kg) or theophylline (P1-receptors antagonist, 0.2 mmol/min/kg) ceased responses to NAD, wherease Ap4A-induced changes were not affected. Pre-treatment with suramin (P2-receptors antagonist, (i.v., bolus - 12 mg/kg followed by 1.2 mg/min/kg) completely abolished the renal effects of Ap4A. We conclude that Ap4A may exert specific action on renal function. It acts different from NAD that modified renal function through its hydrolysis product - adenosine. Ap4A might reduce glomerular filtration rate and evoke natriuresis and diuresis, and its effects are probably mediated through stimulation of P2-receptors.

Trichloroethylene metabolism in rats treated with acetylsalicylic acid and toluene

63%

Orlowski J. , Zielinska-Psuja B. , Kowalowka-Zawieja J. , Dobrogowska J. , Adamek A.

2000

tom 08

nr 2