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

Author:
Nimmu, Narendra Varma, Arnipalli, M. K. Swamy, Appu, Keerthi, Khalid, Sara, Ramisetti, Nageswara Rao
Source:
Chromatographia 2018 v.81 no.11 pp. 1551-1557
ISSN:
0009-5893
Subject:
acetic acid, acetonitrile, ammonium acetate, buffers, drugs, hydrochlorothiazide, liquid chromatography, monitoring, oral administration, pH, pharmacokinetics, rats, tandem mass spectrometry, urine
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.
Agid:
6178382