Laboratory of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico Carlo Besta, 20133 Milano, Italy.
Department of Medicine, Surgery and Dentistry "Scuola Medica Salernitana", University of Salerno, Baronissi, 84081 Salerno, Italy.
Molecules. 2023 May 23;28(11):4264. doi: 10.3390/molecules28114264.
Levodopa (L-DOPA) treatment, combined with the administration of dopa-decarboxylase inhibitors (DDCIs), is still the most effective symptomatic treatment of Parkinson's disease (PD). Although its efficacy in the early stage of the disease has been confirmed, its complex pharmacokinetics (PK) increases the variability of the intra-individual motor response, thus amplifying the risk of motor/non-motor fluctuations and dyskinesia. Moreover, it has been demonstrated that L-DOPA PK is strongly influenced by several clinical, therapeutic, and lifestyle variables (e.g., dietary proteins). L-DOPA therapeutic monitoring is therefore crucial to provide personalized therapy, hence improving drug efficacy and safety. To this aim, we have developed and validated an ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to quantify L-DOPA, levodopa methyl ester (LDME), and the DDCI carbidopa in human plasma. The compounds were extracted by protein precipitation and samples were analyzed with a triple quadrupole mass spectrometer. The method showed good selectivity and specificity for all compounds. No carryover was observed, and dilution integrity was demonstrated. No matrix effect could be retrieved; intra-day and inter-day precision and accuracy values met the acceptance criteria. Reinjection reproducibility was assessed. The described method was successfully applied to a 45-year-old male patient to compare the pharmacokinetic behavior of an L-DOPA-based medical treatment involving commercially available extracts and an LDME/carbidopa (100/25 mg) formulation.
左旋多巴（L-DOPA）治疗联合多巴胺脱羧酶抑制剂（DDCIs）的给药仍然是治疗帕金森病（PD）最有效的对症治疗方法。虽然其在疾病早期的疗效已得到证实，但它复杂的药代动力学（PK）增加了个体内运动反应的可变性，从而放大了运动/非运动波动和运动障碍的风险。此外，已经证明 L-DOPA PK 受到多种临床、治疗和生活方式变量（例如饮食蛋白）的强烈影响。因此，L-DOPA 治疗监测对于提供个性化治疗至关重要，从而提高药物疗效和安全性。为此，我们开发并验证了一种超高效液相色谱-串联质谱（UHPLC-MS/MS）方法，用于定量人血浆中的左旋多巴、左旋多巴甲酯（LDME）和 DDCI 卡比多巴。通过蛋白质沉淀提取化合物，并用三重四极杆质谱仪分析样品。该方法对所有化合物均显示出良好的选择性和特异性。未观察到交叉污染，并且证明了稀释完整性。未检测到基质效应；日内和日间精密度和准确度值符合验收标准。评估了再进样重现性。该方法成功应用于 45 岁男性患者，比较了涉及市售提取物的基于 L-DOPA 的药物治疗和 LDME/卡比多巴（100/25 mg）制剂的药代动力学行为。
