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Alternative LC–MS–MS Method for Simultaneous Determination of Proguanil, Its Active Metabolite in Human Plasma and Application to a Bioequivalence Study

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Abstract

An alternative rapid and sensitive liquid chromatography–tandem mass spectrometry method has been developed and validated for simultaneous analysis of proguanil (PRO) and cycloguanil (CYC) in human plasma. The analytes were extracted from human plasma by solid phase extraction. Riluzole (RIL) was used as an internal standard for proguanil and cycloguanil. A HyPURITY Advance C18 column provided chromatographic separation of analytes followed by detection with mass spectrometry. The method involves simple isocratic chromatography conditions and mass spectrometric detection in the positive ionization mode using an API-4000 system. The proposed method has been validated with linear range of 1.5–150.0 ng mL−1 for PRO and 0.5–50.0 ng mL−1 for CYC. The inter-run and intra-run precision values are within 2.54, 9.19% for PRO and 1.99, 10.69% for CYC at LOQ levels. The overall recoveries for PRO and CYC were 102.52 and 106.72%, respectively. Total elution time was as low as 2.50 min. This validated method was used successfully for analysis of plasma samples from a bioequivalence study.

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Acknowledgments

The authors are indebted to Prof. R. T. Sane, Dr. Vikas Vaidya, Mr. Nelson Varghese and Mr. Sudhir Pawar for their continuous support and for providing the laboratory facilities required for this assay.

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Authors and Affiliations

  1. Department of Chemistry, Mithibai College of Arts, Chaun Institute of Science & Amrutben Jivanlal College of Commerce and Economics, Vile Parle (W), Mumbai, 400056, India

    Satish G. Pingale & Kiran V. Mangaonkar

  2. Drug Monitoring Research Institute, Rabale 400701, Navi Mumbai, India

    Satish G. Pingale, Ketan K. Nerurkar, Ajit M. Padgaonkar & Uttam D. Pawar

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  1. Satish G. Pingale
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  2. Ketan K. Nerurkar
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  3. Ajit M. Padgaonkar
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  4. Uttam D. Pawar
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  5. Kiran V. Mangaonkar
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Correspondence to Kiran V. Mangaonkar.

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Pingale, S.G., Nerurkar, K.K., Padgaonkar, A.M. et al. Alternative LC–MS–MS Method for Simultaneous Determination of Proguanil, Its Active Metabolite in Human Plasma and Application to a Bioequivalence Study. Chroma 70, 1095–1102 (2009). https://doi.org/10.1365/s10337-009-1259-9

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