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  • P-ISSN2233-4203
  • E-ISSN2093-8950
  • ESCI, SCOPUS, KCI

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  • P-ISSN 2233-4203
  • E-ISSN 2093-8950

A Sensitive, Efficient, and Cost-Effective Method to Determine Rotigotine in Rat Plasma Using Liquid-Liquid Extraction (LLE) and LC-MRM

A Sensitive, Efficient, and Cost-Effective Method to Determine Rotigotine in Rat Plasma Using Liquid-Liquid Extraction (LLE) and LC-MRM

Mass Spectrometry Letters / Mass Spectrometry Letters, (P)2233-4203; (E)2093-8950
2022, v.13 no.4, pp.146-151
https://doi.org/10.5478/MSL.2022.13.4.146
Ji Seong Kim (Dankook University)
Yong Jin Jang (Dankook University)
Jin Hee Kim (Dankook University)
Jin Hwan Kim (Dankook University)
Jae Hee Seo (Dankook University)
Il-Ho Park (Sahmyook University)
Myung Joo Kang (Dankook University)
Yong Seok Choi (Dankook University)
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초록

Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson’s disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH- DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over pre- vious methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00–115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the develop- ment of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

keywords
rotigotine, multiple reaction monitoring, liquid-liquid extraction, rat plasma, pharmacokinetics

Abstract

Rotigotine (RTG) is a non-ergot dopamine agonist used to manage the early stage of Parkinson’s disease (PD) as transdermal patch. However, the poor medication compliance of PD patients and skin issues related with repeated applications of RTG patches lead to the search for alternative formulations and it also requires appropriate analytical methods for their in vivo evaluation. Thus, here, a sensitive, efficient, and cost-effective method to determine RTG in rat plasma using liquid-liquid extraction (LLE) and multiple reaction monitoring was developed. The use of 20 µL of rat plasma for sample treatment, 8-OH- DPAT as the internal standard, and methyl tert-butyl ether as the LLE solvent in the present method gives it advantages over pre- vious methods for the analysis of RTG in biological samples. The good analytical performance of the developed method was confirmed in specificity, linearity (the coefficient of determination ≥0.999 within 0.1-100 ng/mL), sensitivity (the lower limit of quantitation at 0.1 ng/mL), accuracy (81.00–115.05%), precision (≤10.75%), and recovery (81.00-104.48%) by following the FDA guidelines. Finally, the applicability test of the validated method to the in vivo evaluation of a RTG formulation showed that the present method is the only method which can be accurately applied to that longer than 24 hours, critical for the develop- ment of formulations with reduced dosing frequencies. Therefore, the present method could contribute to the development of new RTG formulations helpful to people suffering from PD.

keywords
rotigotine, multiple reaction monitoring, liquid-liquid extraction, rat plasma, pharmacokinetics


투고일Submission Date
2022-12-12
수정일Revised Date
2022-12-20
게재확정일Accepted Date
2022-12-20
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