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. 2015 Feb;5(1):1-11.
doi: 10.1016/j.jpha.2014.08.001. Epub 2014 Aug 12.

Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC-MS/MS

Nejal M Bhatt  1 , Vijay D Chavada  1 , Daxesh P Patel  1 , Primal Sharma  1 , Mallika Sanyal  2 , Pranav S Shrivastav  1
Affiliations

Determination of cilostazol and its active metabolite 3,4-dehydro cilostazol from small plasma volume by UPLC-MS/MS

Nejal M Bhatt et al. J Pharm Anal. 2015 Feb.

Abstract

A simple, rapid and sensitive ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed for the simultaneous determination of cilostazol and its pharmacologically active metabolite 3,4-dehydro cilostazol in human plasma using deuterated analogs as internal standards (ISs). Plasma samples were prepared using solid phase extraction and chromatographic separation was performed on UPLC BEH C18 (50 mm×2.1 mm, 1.7 µm) column. The method was established over a concentration range of 0.5-1000 ng/mL for cilostazol and 0.5-500 ng/mL for 3,4-dehydro cilostazol. Intra- and inter-batch precision (% CV) and accuracy for the analytes were found within 0.93-1.88 and 98.8-101.7% for cilostazol and 0.91-2.79 and 98.0-102.7% for the metabolite respectively. The assay recovery was within 95-97% for both the analytes and internal standards. The method was successfully applied to support a bioequivalence study of 100 mg cilostazol in 30 healthy subjects.

Keywords: 3,4-dehydro cilostazol; Cilostazol; High throughput; Sensitive; UPLC−MS/MS.

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Figures

Fig. 1
Fig. 1
Product ion mass spectra in the positive ionization mode for (A) cilostazol (m/z 370.3→288.3) and (B) cilostazol-d11, IS (m/z 381.2→288.3).
Fig. 2
Fig. 2
Product ion mass spectra in the positive ionization mode for (A) 3,4-dehydro cilostazol (m/z 368.2→286.3) and (B) 3,4-dehydro cilostazol-d11, IS (m/z 379.2→286.2).
Fig. 3
Fig. 3
Representative chromatograms of cilostazol (m/z 370.3→288.3) and cilostazol-d11 (m/z 381.2→288.3) in (A) blank plasma, (B) analytes at LLOQ and (C) real subject sample at Cmax after administration of 100 mg dose of cilostazol tablet.
Fig. 4
Fig. 4
Representative chromatograms of 3,4-dehydro cilostazol (m/z 368.2→286.3) and 3,4-dehydro cilostazol-d11 (m/z 379.2→286.2) in (A) blank plasma, (B) analytes at LLOQ and (C) real subject sample at Cmax after administration of 100 mg dose of cilostazol tablet.
Fig. 5
Fig. 5
Mean plasma concentration–time profile of (A) cilostazol and (B) 3,4-dehydro cilostazol after oral administration of test (100 mg cilostazol tablets from Aché Laboratórios Farmacêuticos, Brazil) and reference (Cebralat®, 100 mg of cilostazol tablets from Libbs Pharmaceuticals Ltd., Brazil) formulations to 30 healthy Indian subjects under fasting condition.
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