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LC–MS/MS Determination of Antihypertension Drugs in Rat Plasma and Urine: Applications to Pharmacokinetics

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Abstract

A sensitive, rapid and reproducible LC–MS/MS method for the determination of olmesartan (OLM), amlodipine (ALM) and hydrochlorothiazide (HCZ) in rat plasma and urine has been developed and validated. Irbesartan (IRB) was used as an internal standard. The analytes were separated on a Waters XTerra-C18 column using gradient elution with acetonitrile and 10 mM ammonium acetate buffer (pH 3.5, adjusted with acetic acid) at a flow rate of 1.0 mL min−1. The three analytes were ionized by positive ion electrospray using multiple-reaction monitoring (MRM) mode to monitor precursor → product ion transitions m/z 447.31 → 234.97 for OLM, 408.87 → 238.18 for AML and 290.1 → 204.85 for HCZ. The specificity, matrix effect, recovery, sensitivity, linearity, accuracy, precision, and stabilities were all validated over the concentration range 0.4–100 ng mL−1 for AML, 0.2–100 ng mL−1 for OLM, 0.1–100 ng mL−1 for HCZ. The mean concentrations (Cmax) are 10.32, 587, and 3.4 for OLM, ALM, and HCZ, respectively, by the oral administration of 15 mg kg−1 of each analyte.

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Acknowledgements

The authors thank Director, IICT, for encouragement and permission to communicate the manuscript for publication. N. Narendra Varma and A. M. K. Swamy thank the University Grants Commission (UGC) and Council of Scientific and Industrial Research (CSIR), New Delhi, India, for research fellowship.

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Authors and Affiliations

  1. Analytical Chemistry Division, Discovery Laboratory, Indian Institute of Chemical Technology, Tarnaka, Hyderabad, 500 607, India

    Narendra Varma Nimmu, M. K. Swamy Arnipalli, Keerthi Appu, Sara Khalid & Nageswara Rao Ramisetti

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  1. Narendra Varma Nimmu
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  2. M. K. Swamy Arnipalli
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  3. Keerthi Appu
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  4. Sara Khalid
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  5. Nageswara Rao Ramisetti
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Correspondence to Narendra Varma Nimmu.

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All the authors declare that they have no conflict of interest.

Ethical approval

All applicable institutional guidelines for the care and use of animals were followed. This study was approved by Institutional Animal Ethical Committee, Indian Institute of Chemical Technology-CSIR Hyderabad-500 007, T.S., India, IAEC approval No. (IICT/45/2017) (Registration No: 97/GO/RBi/S/1999/CPCSEA).

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Nimmu, N.V., Arnipalli, M.K.S., Appu, K. et al. LC–MS/MS Determination of Antihypertension Drugs in Rat Plasma and Urine: Applications to Pharmacokinetics. Chromatographia 81, 1551–1557 (2018). https://doi.org/10.1007/s10337-018-3618-x

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  • DOI: https://doi.org/10.1007/s10337-018-3618-x

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