A simple, selective and sensitive method based on high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC–MS/MS) has been developed for the determination of dapaconazole in human plasma using tioconazole as internal standard. The drugs were extracted from plasma by liquid–liquid extraction with ether/hexane (80/20, v/v). The chromatography separation was performed on a Genesis® C18 reversed phase analytical column 4 μm (100 × 2.1 mm i.d.) with a mobile phase of methanol/acetonitrile/water (80/10/10, v/v/v) + ammonium acetate (0.5 mM). Dapaconazole was quantified using a mass spectrometer with an electrospray source in the ESI positive mode (ES+) configured for multiple reaction monitoring (MRM) to monitor the transitions 415.1 > 159.2 and 387.0 > 131.0 for dapaconazole and tioconazole, respectively. The method had a chromatography run time of 3.8 min and a linear calibration curve over the range 0.2–100 ng/mL (r = 0.9998). The lower limit of quantification (LLOQ) was 0.2 ng/mL. The precision and accuracy values of the assay were within ±10%. The stability tests indicate no significant degradation under the conditions of the experiment. This method was used for a phase I study of topical administration of dapaconazole tosylate in healthy human male volunteers.

Quantification of dapaconazole in human plasma using high-​performance liquid chromatography coupled to tandem mass spectrometry: Application to a phase I study

PERISSUTTI, ELISA;FRECENTESE, FRANCESCO;
2014

Abstract

A simple, selective and sensitive method based on high-performance liquid chromatography coupled to tandem mass spectrometry (HPLC–MS/MS) has been developed for the determination of dapaconazole in human plasma using tioconazole as internal standard. The drugs were extracted from plasma by liquid–liquid extraction with ether/hexane (80/20, v/v). The chromatography separation was performed on a Genesis® C18 reversed phase analytical column 4 μm (100 × 2.1 mm i.d.) with a mobile phase of methanol/acetonitrile/water (80/10/10, v/v/v) + ammonium acetate (0.5 mM). Dapaconazole was quantified using a mass spectrometer with an electrospray source in the ESI positive mode (ES+) configured for multiple reaction monitoring (MRM) to monitor the transitions 415.1 > 159.2 and 387.0 > 131.0 for dapaconazole and tioconazole, respectively. The method had a chromatography run time of 3.8 min and a linear calibration curve over the range 0.2–100 ng/mL (r = 0.9998). The lower limit of quantification (LLOQ) was 0.2 ng/mL. The precision and accuracy values of the assay were within ±10%. The stability tests indicate no significant degradation under the conditions of the experiment. This method was used for a phase I study of topical administration of dapaconazole tosylate in healthy human male volunteers.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/605706
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 6
  • ???jsp.display-item.citation.isi??? 4
social impact