Abstract
Purpose: To establish a sensitive and rapid method for the determination of the tissue distribution of 3-hydroxy-1,2-dimethyl-4-pyridone (L1) in vivo, and its plasma protein binding capacity.Methods: This study optimized a reverse-phase HPLC method for specific and sensitive determination of L1 as well as its plasma and tissue distributions. The optimized method was used to determine the plasma protein-binding capacity of L1 in Wistar rats.Results: A rapid, sensitive and simple HPLC-DAD method was established for studying the plasma and tissue distribution of L1. Following TI administration, its liver concentrations peaked at 60 min and 360min, followed 360 min later with peak level in the kidney (second highest). The L1 concentration was significantly lower after 360 min than after 60 min, and values of its mean binding to plasma proteins was 5.2 % at different L1 concentrations.Conclusion: These results indicate that L1 is a drug with rapid-absorption and rapid-elimination thath is distributed widely in vivo in rats. Moreover, the drug has a weak plasma protein-binding capacity.
 Keywords: 3-Hydroxy-1,2-dimethyl-4-pyridone, Distribution, Alzheimer’s disease, Therapy
Highlights
Aluminum is associated with chronic toxicity, with the nervous system as its main target [1]
Studies have shown that aluminum is a possible risk factor for some neurodegenerative illnesses, including Alzheimer’s disease [2, 3]. 3-Hydroxy1,2-dimethyl-4-pyridone (L1) is an orally-active iron chelator which is used for the treatment of iron overload [4]
Since the mobile phase and the impurity in plasma interfere with the detection of L1 at short wavelengths, 278 nm was chosen as the detection wavelength in order to get better sensitivity and accuracy
Summary
Aluminum is associated with chronic toxicity, with the nervous system as its main target [1]. Blank plasma (1 mL) was put into a dialysis bag, and placed in 10 mL of different concentrations of L1 at 37 °C. The plasma protein binding of L1 (f) was calculated using equation: Fifty male Wistar rats (mean weight = 325 ± 20 g) were obtained from the Laboratory Animal Center, Shandong University. The anticoagulated blood samples were used for determination of plasma protein binding capacity of L1. The mobile phase consisted of acetonitrile-phosphate buffer (pH = 3) at volume ratios of 8:92 for plasma, and 1:9 for tissue homogenates and extra-dialysate. A flow rate of 1.0 mL/min was used In this measurement, 1 mL (V1) of phosphate buffer (pH = 7.4) was put into a dialysis bag, and placed in 10 mL (V2) of different concentrations (c3) of L1 at 37 °C for 4 h. Statistical significance of difference was fixed at p < 0.05
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