Simple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma, urine and dialysate

doi:10.1016/S0378-4347(97)00489-1

Journal of Chromatography B: Biomedical Sciences and Applications

Volume 704, Issues 1–2, 19 December 1997, Pages 374-378

https://doi.org/10.1016/S0378-4347(97)00489-1 Get rights and content

Abstract

A simple high-performance liquid chromatographic (HPLC) method was developed for the determination of losartan and its E-3174 metabolite in human plasma, urine and dialysate. For plasma, a gradient mobile phase consisting of 25 mM potassium phosphate and acetonitrile pH 2.2 was used with a phenyl analytical column and fluorescence detection. For urine and dialysate, an isocratic mobile phase consisting of 25 mM potassium phosphate and acetonitrile (60:40, v/v) pH 2.2 was used. The method demonstrated linearity from 10 to 1000 ng/ml with a detection limit of 1 ng/ml for losartan and E-3174 using 10 μl of prepared plasma, urine or dialysate. The method was utilized in a study evaluating the pharmacokinetic and pharmacodynamic effects of losartan in patients with kidney failure undergoing continuous ambulatory peritoneal dialysis (CAPD).

Introduction

Losartan (2-n-butyl-4-chloro-5-hydroxymethyl-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole, potassium salt) is an orally active selective AT₁-receptor antagonist employed in the management of essential hypertension 1, 2, 3. The metabolite E-3174 (2-n-butyl-4-chloro-1-[(2′-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]imidazole-5-carboxylic acid) is a pharmacologically active metabolite of losartan 4, 5. One HPLC method published to date for measurement of losartan and E-3174 utilized a conventional analytical column (e.g., 4.6 mm internal diameter), an internal standard, and tedious liquid–liquid extraction [6]. The method detailed in the present communication utilizes a simple sample preparation step for each matrice and does not require an internal standard. In addition, this method employs current HPLC midbore column technology which provides not only excellent sensitivity but also reduces mobile phase requirements.

Section snippets

Chemicals

Losartan (CAS 124750-99-8) and E-3174 were kindly provided by Dupont Merck Pharmaceutical Company (Wilmington, DE, USA). o-Phosphoric acid (85%) was HPLC grade and purchased from Fisher Scientific (Fair Lawn, NJ, USA). Acetonitrile was Optima HPLC grade and purchased from Fisher Scientific. Ultrapure distilled and deionized water was prepared in-house and filtered prior to use. Peritoneal dialysis solution consisted of 2.5% dextrose (w/v), 0.5% NaCl (w/v), 0.005% MgCl₂ (w/v), 0.018% CaCl₂

Chromatography

The method demonstrated excellent chromatographic selectivity with no endogenous plasma interferences at the retention times for losartan and E-3174 (7.3 and 9.3 min, respectively) (Fig. 1A). Chromatograms of prepared blank human plasma containing low (10 ng/ml) and high (1000 ng/ml) concentrations of losartan and E-3174 (Fig. 1B,C, respectively) indicated good detector response and baseline resolution from endogenous substances with an analytical run time of 20 min. A typical chromatogram for

Conclusion

A simple method was developed for evaluating losartan and its E-3174 metabolite in plasma, urine and dialysate. We employed a precipitate and shoot method for plasma samples, a dilute and shoot technique for urine samples and neat injections for dialysate samples. This eliminated both the need for sample extractions and an internal standard, thus making this method extremely cost effective. In addition, this method used current midbore HPLC column technology which afforded excellent sensitivity

Acknowledgements

The authors thank Dupont Merck Pharmaceutical Company for providing standard material for losartan and E-3174.

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Short communicationSimple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma, urine and dialysate

Abstract

Introduction

Section snippets

Chemicals

Chromatography

Conclusion

Acknowledgements

J. Chromatogr.

Clin. Pharmacol. Ther.

J. Hypertension

Short communication
Simple high-performance liquid chromatographic method for determination of losartan and E-3174 metabolite in human plasma, urine and dialysate