Simultaneous estimation of ZY-19489 and its active metabolite ZY-20486 in human plasma using LC-MS/MS, a novel antimalarial compound

  • Bioanalysis. 2021 Dec;13(23):1761-1777. doi: 10.4155/bio-2021-0194.
Ashok M Ghoghari  1 ,  Harilal V Patel  1 ,  Nisarg N Nayak  1 ,  Tariq H Mansuri  1 ,  Soma M Pillai  1 ,  Mukul R Jain  1 ,  Hardik B Patel  2 ,  Kevin Kansagra  2 ,  Ilaria Di Resta  3 ,  Jörg Möhrle  3 ,  Deven V Parmar  4
Affiliations
  • 1. Bioanalytical Laboratory, Zydus Research Centre, Ahmedabad, Gujarat, India.
  • 2. Clinical Research, Zydus Research Centre, Ahmedabad, Gujarat, India.
  • 3. Medicines for Malaria Venture, Geneva, Switzerland.
  • 4. Zydus Therapeutics Inc., NJ 08534, USA.
PMID: 34779650 DOI: 10.4155/bio-2021-0194
Abstract

Aim: ZY-19489 is a new antimalarial drug candidate and selective LC-MS/MS method was established for estimation of ZY-19489 and its metabolite in human plasma. Materials & methods: LLE was employed for extraction, mass spectrometric quantification performed using positive ionization mode and DCP-IMP was used as an internal standard. The chromatographic separation was achieved using mobile phase 5 mM ammonium formate in water and 0.1% v/v ammonia solution in methanol:acetonitrile (90:10% v/v) and column Agilent Zorbex Extended C18, 3.5 μm, 100 × 4.6 mm with a 6-min run time. Results: The calibration curve of ZY-19489 was linear over range 1-500 ng/ml and 2-200 ng/ml for metabolite. Assay was reproducible, selective and devoid of matrix effect. Conclusion: The validated assay was implemented for clinical sample analysis derived from healthy human subjects and parasitemia-induced subjects.

Keywords
LC–MS/MS; ZY-19489; ZY-20486; human plasma; method validation.
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