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Stability-indicating reversed-phase HPLC method development and characterization of impurities in vortioxetine utilizing LC-MS, IR and NMR.

Stability-indicating reversed-phase HPLC method development and characterization of impurities in vortioxetine utilizing LC-MS, IR and NMR.

Journal of pharmaceutical and biomedical analysis (2015-09-29)

Lei Liu, Na Cao, Xingling Ma, Kaihe Xiong, Lili Sun, Qiaogen Zou, Lili Yao

ABSTRACT

The current study reports the development and validation of a stability-indicating reversed phase HPLC method for the separation and identification of potential impurities in vortioxetine, a recently developed antidepressant. The structures of a new compound and four process-related impurities formed during the synthesis were characterized and confirmed by NMR, MS, and IR spectroscopy analyses. The most probable formation mechanisms of the impurities identified were proposed. Based on the characterization data, the new compound was proposed to be 1-[4-[(2,4-dimethylphenyl)thio]phenyl]-piperazine. In addition, an efficient chromatographic method was optimized to separate and quantify the impurities, which were obtained in the 0.05-0.75 μg/mL range. The developed HPLC method was validated with respect to accuracy, precision, linearity, robustness, and limits of detection and quantitation.

MATERIALS

Product Number

Brand

Product Description

Sigma-Aldrich

Potassium bromide, BioUltra, ≥99.5% (AT)

Sigma-Aldrich

Acetonitrile solution, contains 0.05 % (v/v) trifluoroacetic acid

Sigma-Aldrich

Acetonitrile solution, contains 0.1 % (v/v) trifluoroacetic acid, suitable for HPLC

Sigma-Aldrich

Potassium bromide, anhydrous, powder, 99.999% trace metals basis

Sigma-Aldrich

Potassium bromide, anhydrous, powder, 99.95% trace metals basis

Sigma-Aldrich

Acetonitrile solution, contains 0.1 % (v/v) formic acid, suitable for HPLC

Sigma-Aldrich

Potassium bromide, BioXtra, ≥99.0%

Sigma-Aldrich

Acetonitrile solution, contains 0.05 % (w/v) ammonium formate, 5 % (v/v) water, 0.1 % (v/v) formic acid, suitable for HPLC

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Acetonitrile solution, contains 10.0% acetone, 0.05% formic acid, 40.0% 2-propanol

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Potassium bromide, JIS special grade, 99.0-100.2%

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Potassium bromide, ACS reagent, ≥99.0%

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Potassium bromide, anhydrous, free-flowing, Redi-Dri^™, ACS reagent, ≥99%

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Potassium bromide, anhydrous, free-flowing, Redi-Dri^™, ReagentPlus^®, ≥99%

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1-(4-bromophenyl)piperazine, 95%

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Potassium bromide, ReagentPlus^®, ≥99.0%

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Potassium bromide, FT-IR grade, ≥99% trace metals basis

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Acetonitrile, HPLC Plus, ≥99.9%, poly-coated bottles

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Acetonitrile, for residue analysis, JIS 5000

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Acetonitrile, for chromatography

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Acetonitrile, SAJ first grade, ≥99.0%

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Acetonitrile, JIS special grade, ≥99.5%

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Acetonitrile, ≥99.8%, for residue analysis, JIS 300

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Acetonitrile, electronic grade, 99.999% trace metals basis

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2-Bromoiodobenzene, 99%

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Piperazine, ReagentPlus^®, 99%

Supelco

Acetonitrile, HPLC grade, ≥99.93%

Sigma-Aldrich

Acetonitrile, ≥99.5%, ACS reagent

Sigma-Aldrich

Acetonitrile, anhydrous, 99.8%

Sigma-Aldrich

Acetonitrile, biotech. grade, ≥99.93%

Sigma-Aldrich

Trifluoroacetic acid, SAJ special grade, ≥99.0%