Abstract

Levodopa is widely administered orally in clinical treatment of Parkinson’s disease; however, due to levodopa various oral absorption and low bioavailability, intranasal delivery seems to be a suitable alternative route of administration. Pluronic F-127 is a thermosensitive polymer, which can form gel at nasal cavity temperature and increase drug residence time. In this study, a rapid High Performance Liquid Chromatography (HPLC) method was validated in presence of internal standard to determine pharmacokinetic parameters following levodopa administration to rats in three different intravenous solution, intranasal solution and intranasal thermosensitive gel groups. A precised (96.7%) and accurate (95.0%) HPLC method was validated at low UltraViolet (UV) wavelength of 208 nm that showed limit of detection and limit of quantitation of 59 and 177 ng/mL, respectively. Specificity results showed no interference for levodopa with endogenous serum materials, and serum extraction efficacy was 93%. Pharmacokinetic parameters including bioavailability of 75 and 85% with mean residence time of 78 and 94 min were estimated for intranasal solution and thermosensitive gel using the validated HPLC method, which indicated that levodopa nasal gel may be a good alternative with appropriate pharmacokinetic outcome. Therefore, the validated levodopa HPLC analysis method at low UV wavelength was efficiently applied in pharmacokinetic study.

中文翻译：

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快速高效液相色谱法在低紫外线波长下定量左旋多巴：药代动力学研究在大鼠经鼻输送后的应用

抽象的

左旋多巴广泛用于帕金森氏病的临床治疗。然而，由于左旋多巴的各种口服吸收和低生物利用度，鼻内给药似乎是合适的替代给药途径。Pluronic F-127是一种热敏聚合物，可以在鼻腔温度下形成凝胶并增加药物停留时间。在本研究中，在三种不同的静脉内溶液，鼻内溶液和鼻内热敏凝胶组中，左旋多巴对大鼠给药后，在有内标物存在的情况下验证了快速高效液相色谱（HPLC）方法以确定药代动力学参数。精确（96.7％）和准确（95。（0％）HPLC方法在208 nm的低紫外线（UV）波长下得到验证，该波长分别显示出检测限和定量限59和177 ng / mL。特异性结果显示左旋多巴对内源性血清物质无干扰，血清提取效率为93％。经验证的HPLC方法估计了鼻内溶液和热敏凝胶的药代动力学参数，包括生物利用度为75和85％，平均停留时间为78和94分钟，这表明左旋多巴鼻凝胶可能是具有适当药代动力学结果的良好选择。因此，已验证的低紫外线波长左旋多巴HPLC分析方法可有效地用于药代动力学研究。血清提取率为93％。经验证的HPLC方法估计了鼻内溶液和热敏凝胶的药代动力学参数，包括生物利用度为75和85％，平均停留时间为78和94分钟，这表明左旋多巴鼻凝胶可能是具有适当药代动力学结果的良好选择。因此，已验证的低紫外线波长左旋多巴HPLC分析方法可有效地用于药代动力学研究。血清提取率为93％。经验证的HPLC方法估计了鼻内溶液和热敏凝胶的药代动力学参数，包括生物利用度为75和85％，平均停留时间为78和94分钟，这表明左旋多巴鼻凝胶可能是具有适当药代动力学结果的良好选择。因此，已验证的低紫外线波长左旋多巴HPLC分析方法可有效地用于药代动力学研究。