Valsartán

Sci Pharm. 2008; 76: 439–450 doi:10.3797/scipharm.0808-01 © Österreichische Apotheker-Verlagsgesellschaft m. b. H., Vienna, Austria Reproduction is permitted for non-commercial purposes.

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Rapid Quantification of Valsartan in Human Plasma by Liquid Chromatography using a Monolithic Column and a Fluorescence Detection: Application for Pharmacokinetic Studies
Afshin ZARGHI * 1, AlirezaSHAFAATI 1, Seyed Mohsen FOROUTAN 2, Hooman MOVAHED 3
1

Department of Pharmaceutical Chemistry, School of Pharmacy, Shahid Beheshti University (M. C), Tehran, Iran
2

Department of Pharmaceutics, School of Pharmacy, Shahid Beheshti University (M. C), Tehran, Iran

3

Noor Research and Educational Institute, Tehran, Iran

Abstract
A rapid high-performance liquid chromatographic (HPLC)method using a monolithic column has been developed for determination of valsartan in human plasma. The assay is based on protein precipitation using acetonitrile and fluorescence detection. The assay enables the measurement of valsartan for therapeutic drug monitoring with a minimum quantification limit of 20 ngml-1. The method involves simple, one-step extraction procedure and analytical recoverywas nearly complete. The separation was carried out in reversed-phase conditions using a Chromolith Performance (RP-18e, 100×4.6 mm) column with an isocratic mobile phase consisting of 0.01 M disodium hydrogen phosphate buffer-acetonitrile (60:40 v/v) adjusted to pH 3.5 with diluted phosphoric acid. The excitation and emission wavelengths were set at 230 and 295 nm, respectively. The calibrationcurve was linear over the concentration range 20-2000 ngml-1. The coefficients of variation for inter-day and intra-day assay were found to be less than 6%. The assay was applied for the analysis of blood samples from a pharmacokinetic study.
* Corresponding author: Tel.: ++98-21- 88773521; Fax: ++98-21-88795008. E-mail: azarghi@yahoo.com (A. Zarghi).

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KeywordsValsartan • Plasma • HPLC • Monolithic column • Pharmacokinetic study

Introduction
Valsartan is a potent and specific competitive angiotensin II antagonist which is used in the management of hypertension. Valsartan is rapidly absorbed following oral administration, with a rather poor bioavailability of about 23%. Peak plasma concentrations of valsartan occur 2 to 4 hours after ingestion. The drugis not significantly metabolized and is excreted mainly via the bile as unchanged drug [1, 2]. Several high-performance liquid chromatographic (HPLC) methods are available for determination of valsartan in plasma. All published assays employ native fluorescence of valsartan and use fluorimetric detection [3–10]. The sample preparation involves either liquid–liquid extraction with methyl-tert-butylether [3] and ethyl acetate [4] or solid-phase extraction using C8 [6–8] or cyclohexyl [3, 8] cartridges. The limit of quantification (LOQ) in these procedures is 5–130 ngml-1, run times are typically 10–30 min. Macek et al [10] reported a rapid HPLC/fluorescence method for analysis of valsartan in human plasma. However, this method had low sensitivity (LOQ = 100 ngml-1) and internal standard wasnot used. Accordingly, available pharmacokinetic profiles were only provided for the higher dose (160 or 320 mg) subjects. Recently, a LC-MS/MS method has been reported for the analyses of valsartan in human plasma by Koseki et al [11]. This method is highly selective and very sensitive, with low LOQ of 2 ngml-1. However, this method is not practicable for most laboratories because of its specialanalytical requirements and financial reasons. Moreover, some purification steps are necessay before the samples are injected into chromatographic system such as liquid-liquid extraction, solid phase extraction, etc. Monolithic silica columns as stationary phases exhibit a tailor-made bimodal pore structure with both macropores or through pores and mesopores. The most unique feature of these...