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Determination of levodopa by chromatography-based methods in biological samples: a review

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Abstract

Levodopa (l-DOPA) is the most effective drug for Parkinson’s disease; however, various side effects occur during therapy. l-DOPA metabolites and the high cumulative dose of l-DOPA were responsible for its side effects. It is necessary to monitor the concentration of l-DOPA and its metabolites for individualized therapy. This review focuses on l-DOPA analysis by chromatography-based methods in biological matrices. Literature published up to September 2021 was collected in the PubMed, Web of Science, and Embase by using search strategy (“levodopa” OR “l-DOPA”) AND (“chromatography”). A total of 1249 articles were identified and 32 articles were included. The contents for method development and validation were summarized and analyzed. Due to the instability of catecholamines (l-DOPA, dopamine, and 3-O-methyldopa) and carbidopa, antioxidation (0.5 mg sodium metabisulfite for 100 μL sample) and environment temperature control were used alone or in combination to enhance stability. Sample was mainly pretreated by protein precipitation (0.4–0.7 M perchloric acid). Separation was usually achieved using methanol or acetonitrile:water (with formic acid) on C18 columns. Mass spectrometry, electrochemical detector, ultraviolet–visible detector and fluorescence detector were used for detection. For l-DOPA, the calibration range was 2.5–10,000 ng/mL, the matrix effect and its coefficient of variation was 85–115 and –9.0–8.5%, and the recovery was 66.8–127.0%. Without stabilization strategy, l-DOPA was stable in plasma at room temperature for 1–7 h (4–6 h for most studies), at – 70 °C to – 80 °C for 10–20 days and after 3–5 freeze–thaw cycles. With stabilization strategies, the stability of l-DOPA in plasma was significantly improved. Metabolites of l-DOPA and enzyme inhibitors (carbidopa, entacapone, tolcapone and benserazide) were all stable in biological matrix. This study might be useful for researchers to develop their methods for individualized therapy of patients with Parkinson.

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Abbreviations

L-DOPA:

Levodopa

DA:

Dopamine

COMT:

Catechol-O methyltransferase

AADC:

Aromatic amino acid decarboxylase

3-OMD:

3-O-methyldopa

MAO:

Monoamine oxidase

MS:

Mass spectrometry

ED:

Electrochemical detector

UV:

Ultraviolet–visible

FL:

Fluorescence

HPLC:

High performance liquid chromatography

PP:

Protein precipitation

LLE:

Liquid–liquid extraction

SPE:

Solid phase extraction

IS:

Internal standard

LOQ:

Lower limit of quantitation

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Funding

This study was supported by National Key R&D Program of China (2020YFC2008306).

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Authors and Affiliations

  1. Department of Pharmacy, Beijing Tiantan Hospital, Capital Medical University, 119 Nansihuan West Road, Fengtai District, Beijing, 100070, People’s Republic of China

    Ruiqi Jiang, Jiayu Yang, Shenghui Mei & Zhigang Zhao

  2. Department of Clinical Pharmacology, College of Pharmaceutical Sciences, Capital Medical University, Beijing, 100069, People’s Republic of China

    Ruiqi Jiang, Jiayu Yang, Shenghui Mei & Zhigang Zhao

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  1. Ruiqi Jiang
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Correspondence to Shenghui Mei or Zhigang Zhao.

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Jiang, R., Yang, J., Mei, S. et al. Determination of levodopa by chromatography-based methods in biological samples: a review. ANAL. SCI. 38, 1009–1017 (2022). https://doi.org/10.1007/s44211-022-00132-4

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