Determination of Perampanel in Dried Plasma Spots: Applicability to Therapeutic Drug Monitoring

Valentina Franco, Katia Baruffi, Roberto Marchiselli Francesca Crema, Cinzia Fattore, Andrea Romigi, De Giorgis Valentina, Elena Tartara, Elia Maurizio, Antonio D'Avolio, Emilio Perucca

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Although therapeutic drug monitoring of antiepileptic drugs (AEDs) is typically based on analysis of plasma samples, alternative matrices such as dried plasma spots (DPSs) may offer specific advantages. The aims of this work were to: i) develop and validate a bioanalytical method for the quantitative determination of the second-generation AED perampanel in DPSs; ii) assess short- and long-term stability of perampanel in DPSs; and iii) test the clinical applicability of the developed method.

METHODS: Two hundred microliters of plasma were dispensed on a glass paper filter and dried. Glass paper filter discs were then inserted into clean tubes. After addition of the internal standard (i.e., promethazine), the analytes were extracted with 5 mL methanol, dried at room temperature (23±2°C), and reconstituted. Separation and quantification were achieved on two serial reverse-phase monolithic columns connected to a UV detector (λ=320 nm).

RESULTS: Calibration curves were linear in the validated concentration range (25-1000 ng/mL). Intra-day and inter-day accuracy were in the range of 99.2-111.4%, whereas intra-day and inter-day precision (CV) ranged from 3.4 to 8.6%. The lowest limit of quantitation was 25 ng/mL. The stability of the analyte in DPSs was assessed and confirmed under different storage conditions. Perampanel concentrations estimated in DPS samples from patients receiving therapeutic doses were equivalent to those measured in plasma samples.

CONCLUSIONS: This simple method enables the quantitation of perampanel in DPSs with adequate accuracy, precision, specificity, and sensitivity. The short- and long-term stability of perampanel in DPSs is highly beneficial for sample shipment or storage at ambient temperature. Moreover, DPSs decreases the costs associated with storage and transportation compared with conventional wet samples.

Original languageEnglish
JournalTherapeutic Drug Monitoring
DOIs
Publication statusE-pub ahead of print - Jul 29 2019

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Drug Monitoring
Anticonvulsants
Glass
perampanel
Promethazine
Temperature
Calibration
Methanol
Costs and Cost Analysis
Sensitivity and Specificity

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Determination of Perampanel in Dried Plasma Spots : Applicability to Therapeutic Drug Monitoring. / Franco, Valentina; Baruffi, Katia; Francesca Crema, Roberto Marchiselli; Fattore, Cinzia; Romigi, Andrea; Valentina, De Giorgis; Tartara, Elena; Maurizio, Elia; D'Avolio, Antonio; Perucca, Emilio.

In: Therapeutic Drug Monitoring, 29.07.2019.

Research output: Contribution to journalArticle

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abstract = "BACKGROUND: Although therapeutic drug monitoring of antiepileptic drugs (AEDs) is typically based on analysis of plasma samples, alternative matrices such as dried plasma spots (DPSs) may offer specific advantages. The aims of this work were to: i) develop and validate a bioanalytical method for the quantitative determination of the second-generation AED perampanel in DPSs; ii) assess short- and long-term stability of perampanel in DPSs; and iii) test the clinical applicability of the developed method.METHODS: Two hundred microliters of plasma were dispensed on a glass paper filter and dried. Glass paper filter discs were then inserted into clean tubes. After addition of the internal standard (i.e., promethazine), the analytes were extracted with 5 mL methanol, dried at room temperature (23±2°C), and reconstituted. Separation and quantification were achieved on two serial reverse-phase monolithic columns connected to a UV detector (λ=320 nm).RESULTS: Calibration curves were linear in the validated concentration range (25-1000 ng/mL). Intra-day and inter-day accuracy were in the range of 99.2-111.4{\%}, whereas intra-day and inter-day precision (CV) ranged from 3.4 to 8.6{\%}. The lowest limit of quantitation was 25 ng/mL. The stability of the analyte in DPSs was assessed and confirmed under different storage conditions. Perampanel concentrations estimated in DPS samples from patients receiving therapeutic doses were equivalent to those measured in plasma samples.CONCLUSIONS: This simple method enables the quantitation of perampanel in DPSs with adequate accuracy, precision, specificity, and sensitivity. The short- and long-term stability of perampanel in DPSs is highly beneficial for sample shipment or storage at ambient temperature. Moreover, DPSs decreases the costs associated with storage and transportation compared with conventional wet samples.",
author = "Valentina Franco and Katia Baruffi and {Francesca Crema}, {Roberto Marchiselli} and Cinzia Fattore and Andrea Romigi and Valentina, {De Giorgis} and Elena Tartara and Elia Maurizio and Antonio D'Avolio and Emilio Perucca",
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T1 - Determination of Perampanel in Dried Plasma Spots

T2 - Applicability to Therapeutic Drug Monitoring

AU - Franco, Valentina

AU - Baruffi, Katia

AU - Francesca Crema, Roberto Marchiselli

AU - Fattore, Cinzia

AU - Romigi, Andrea

AU - Valentina, De Giorgis

AU - Tartara, Elena

AU - Maurizio, Elia

AU - D'Avolio, Antonio

AU - Perucca, Emilio

PY - 2019/7/29

Y1 - 2019/7/29

N2 - BACKGROUND: Although therapeutic drug monitoring of antiepileptic drugs (AEDs) is typically based on analysis of plasma samples, alternative matrices such as dried plasma spots (DPSs) may offer specific advantages. The aims of this work were to: i) develop and validate a bioanalytical method for the quantitative determination of the second-generation AED perampanel in DPSs; ii) assess short- and long-term stability of perampanel in DPSs; and iii) test the clinical applicability of the developed method.METHODS: Two hundred microliters of plasma were dispensed on a glass paper filter and dried. Glass paper filter discs were then inserted into clean tubes. After addition of the internal standard (i.e., promethazine), the analytes were extracted with 5 mL methanol, dried at room temperature (23±2°C), and reconstituted. Separation and quantification were achieved on two serial reverse-phase monolithic columns connected to a UV detector (λ=320 nm).RESULTS: Calibration curves were linear in the validated concentration range (25-1000 ng/mL). Intra-day and inter-day accuracy were in the range of 99.2-111.4%, whereas intra-day and inter-day precision (CV) ranged from 3.4 to 8.6%. The lowest limit of quantitation was 25 ng/mL. The stability of the analyte in DPSs was assessed and confirmed under different storage conditions. Perampanel concentrations estimated in DPS samples from patients receiving therapeutic doses were equivalent to those measured in plasma samples.CONCLUSIONS: This simple method enables the quantitation of perampanel in DPSs with adequate accuracy, precision, specificity, and sensitivity. The short- and long-term stability of perampanel in DPSs is highly beneficial for sample shipment or storage at ambient temperature. Moreover, DPSs decreases the costs associated with storage and transportation compared with conventional wet samples.

AB - BACKGROUND: Although therapeutic drug monitoring of antiepileptic drugs (AEDs) is typically based on analysis of plasma samples, alternative matrices such as dried plasma spots (DPSs) may offer specific advantages. The aims of this work were to: i) develop and validate a bioanalytical method for the quantitative determination of the second-generation AED perampanel in DPSs; ii) assess short- and long-term stability of perampanel in DPSs; and iii) test the clinical applicability of the developed method.METHODS: Two hundred microliters of plasma were dispensed on a glass paper filter and dried. Glass paper filter discs were then inserted into clean tubes. After addition of the internal standard (i.e., promethazine), the analytes were extracted with 5 mL methanol, dried at room temperature (23±2°C), and reconstituted. Separation and quantification were achieved on two serial reverse-phase monolithic columns connected to a UV detector (λ=320 nm).RESULTS: Calibration curves were linear in the validated concentration range (25-1000 ng/mL). Intra-day and inter-day accuracy were in the range of 99.2-111.4%, whereas intra-day and inter-day precision (CV) ranged from 3.4 to 8.6%. The lowest limit of quantitation was 25 ng/mL. The stability of the analyte in DPSs was assessed and confirmed under different storage conditions. Perampanel concentrations estimated in DPS samples from patients receiving therapeutic doses were equivalent to those measured in plasma samples.CONCLUSIONS: This simple method enables the quantitation of perampanel in DPSs with adequate accuracy, precision, specificity, and sensitivity. The short- and long-term stability of perampanel in DPSs is highly beneficial for sample shipment or storage at ambient temperature. Moreover, DPSs decreases the costs associated with storage and transportation compared with conventional wet samples.

U2 - 10.1097/FTD.0000000000000680

DO - 10.1097/FTD.0000000000000680

M3 - Article

C2 - 31365481

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

ER -