Quantification of antihistamine acrivastine in plasma by solid-phase extraction and high-performance liquid chromatography

doi:10.1016/j.jpba.2006.07.009

Journal of Pharmaceutical and Biomedical Analysis

Volume 43, Issue 1, 4 January 2007, Pages 293-297

https://doi.org/10.1016/j.jpba.2006.07.009 Get rights and content

Abstract

An automated solid-phase extraction method was developed for the determination of the H₁-antihistamine acrivastine in plasma samples. Acrivastine was analyzed at the wavelength of 254 nm using a reversed-phase HPLC assay. Both extraction procedure and analytical condition were optimized and validated for maximum recovery and resolution. The developed method was further applied to plasma samples collected from an in vivo pharmacokinetic study in rabbits. The assay was found to be simple, specific, accurate and reproducible.

Introduction

The number of reported cases of allergic disorders has risen substantially during the past quarter of a century. Increased amounts of air pollutants as well as natural environmental allergens, xenobiotics and stress have all been attributed to the increase in incidence of allergic diseases [1], [2]. The severity of an allergic disorder is highly variable among the individuals, and may range from mild discomfort to significant impairment of the quality of life, in some rare cases, even leading to life-threatening conditions. Increases in allergic disorders have already had, and will continue to have a considerable impact on the healthcare resources. Common treatment of allergic disorders, especially allergic rhinitis and uticaria, includes the administration of H₁-antihistamines, medications that reduce or inhibit the release of histamine through negative modulation of the histaminic receptors [3].

Acrivastine [(E)-3-(6-[3-pyrrolidino-1-(4-tolyl)-prop-1E-enyl]-2-pyridyl)-acrylic acid] (Fig. 1A), is a second-generation, non-sedating antihistamine that was derived from the first-generation compound triprolidine (Fig. 1B) [4]. Compared to the earlier antihistamines, the second-generation compounds have been significantly improved pharmacologically and pharmacokinetically, so that they have exhibited better patient compliance and fewer adverse effects, in particular, lower effects on the central nervous system (e.g., sedation, impairment of psychomotor functions) [3], [5]. Various antihistamines have been commercially available for clinical applications for decades; acrivastine (Semprex^® and Semprex^®-D) is one of them that is specifically used for the treatment of allergic rhinitis [6], [7].

Numerous analytical methods have been reported to determine acrivastine in both pharmaceutical preparations and biological specimens. These included derivative spectrophotometry [8], high-performance liquid chromatography with ultraviolet detection (HPLC-UV) [9], gas chromatography with mass spectrometric detection (GC–MS) [10], [11], radioimmunoassay [12], and electrochemical measurement [13]. We have recently reported an HPLC-UV method to simultaneously analyze acrivastine and pseudoephedrine hydrochloride in Semprex^®-D capsules [14]. The assay was found to be accurate, specific, selective, rapid and versatile for use in routine quality control of acrivastine and pseudoephedrine preparations.

For pharmacokinetic and pharmacodynamic evaluation of any medication, a reproducible and simple separation method is a prerequisite for the generation of accurate and reliable study data. Solid-phase extraction has been extensively employed in the pharmaceutical and biomedical analysis, due largely to significant advantages and improvements in automation, reproducibility and high-throughput capability [15], [16]. For acrivastine, however, previous extraction methods were mainly complex and time-consuming, which commonly involved several rounds of extraction and derivatization [11], [12]. They are unable to meet the extensive requirements for investigational and regulatory purposes.

In this study, we developed a simple and reproducible solid-phase extraction procedure to separate acrivastine in the plasma and then used an HPLC-UV assay for the drug measurement. The method was optimized and validated to achieve high accuracy and reliability. The resultant approach was further employed to separate and analyze acrivastine concentrations in plasma samples collected from an in vivo pharmacokinetic study in a rabbit model.

Section snippets

Chemicals

Acrivastine standard and Semprex^®-D capsules were received as gifts from Celltech Pharmaceuticals (Rochester, NY, USA). Diphenhydramine (Fig. 1C), the internal standard, was obtained from Parke-Davis Co. Ltd. (Brockville, Ont., Canada). Concentrated acetic acid, acetonitrile, methanol and sodium acetate trihydrate were purchased from Fisher Scientific (Fair Lawn, NJ, USA). All chemicals and reagents used were either HPLC grade or AC grade. Deionized water was obtained from a Millipore^® Milli-Q

Optimization of SPE procedure

To allow for high-throughput in pharmaceutical and biomedical analysis in support of pharmacokinetic evaluation or clinical trials of new chemical entities, a developed extraction method has to exhibit sufficient robustness and flexibility in its application. The advent of solid-phase extraction has greatly evolved in the past several years, gradually replacing traditional extraction approaches with liquid–liquid manipulation. In addition, solid-phase extraction is particularly advantageous and

Conclusion

The automated solid-phase extraction process that was developed in this study was simple, accurate and reproducible. With the help of an automated computer-controlled program, the extraction process required only minimal sample pretreatment and achieved satisfactory extraction recovery. The method was capable of eliminating unintentional human errors in the operation and facilitating high throughput with a large number of biological samples.

The HPLC assay that was validated for the measurement

Acknowledgements

The authors acknowledge the generous supply of acrivastine pure compound and Semprex^®-D capsules by Celltech Pharmaceuticals and animal study assistance by Dr. Keith Simons of the Faculty of Pharmacy. Research support from the Canada Foundation for Innovation and the University of Manitoba is also acknowledged.

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Identification, synthesis and structural characterization of process related and degradation impurities of acrivastine and validation of HPLC method
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Citation Excerpt :
The combination therapy of acrivastine with pseudoephedrine can show direct effect on the α-adrenergic receptor, used for relieving a variety of symptoms instigated by seasonal allergic coryza like sneezing, nose running, itching, tearing and nasal obstruction. Much study on acrivastine was available in the literature mainly concerning radioimmuno assay [8], determination of acrivastine using gas chromatography [9], its quantification in plasma by solid-phase extraction and high-performance liquid chromatography (HPLC) [10,11] and liquid chromatography-tandem mass spectrometry (LC-MS), and HPLC-UV method for the determination of acrivastine and pseudoephedrine in capsules [12,13]. Spectrofluorimetric, spectrophotometric and colorimetric methods for the determination of acrivastine in spiked human urine and pharmaceuticals [14–19] and electrochemical methods [20,21] were also discussed.
Four impurities (Imp-I–IV) were detected using gradient HPLC method in few laboratory batches of acrivastine in the level of 0.03–0.12% and three impurities (Imp-I–III) were found to be known and one (Imp-IV) was unknown. In forced degradation study, the drug is degraded into four degradation products under oxidation and photolytic conditions. Two impurities (Imp-III and -IV) were concurred with process related impurities whereas Imp-V and -VI were identified as new degradation impurities. Based on LC-ESI/MSⁿ study, the chemical structures of new impurities were presumed as 1-[(2E)-3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}prop-2-en-1-yl]pyrrolidin-1-ium-1-olate (Imp-IV), 1-{[3-(4-methylphenyl)-3-{6-[(1E)-3-oxobut-1-en-1-yl]pyridin-2-yl}oxiran-2-yl]methyl}pyrrolidin-1-ium-1-olate (Imp-V) and 2-[2-(4-methylphenyl)-3-[(1-oxidopyrrolidin-1-ium-1-yl)methyl]oxiran-2-yl]-6-[(1E)-3-oxobut-1-en-1-yl]pyridin-1-ium-1-olate (Imp-VI), and confirmed by their synthesis followed by spectroscopic analysis, IR, NMR (¹H, ¹³C) and mass. An efficient and selective high-performance liquid chromatography method has been developed and resolved well the drug related substances on a Phenomenex Gemini C-18 (250 × 4.6 mm, particle size 5 μm) column. The mobile phase was composed of sodium dihydrogen phosphate (10 mM) and methanol, temperature at 25 °C, and a PDA detector set at 254 nm used for detection. The method was validated with respect to specificity, linearity, precision, accuracy, and sensitivity and satisfactory results were achieved. Identification, synthesis, characterization of impurities and method validation were first reported in this paper.
Development and validation of a rapid stability indicating HPLC-method using monolithic stationary phase and two spectrophotometric methods for determination of antihistaminic acrivastine in capsules
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Simultaneous determination of acrivastine and pseudoephedrine in capsules was carried out using liquid chromatography-tandem mass spectrometry [6], HPLC–UV method [7] and a derivative spectrophotometric procedure [8]. Quantification of antihistamine acrivastine in plasma was done by solid-phase extraction and high-performance liquid chromatography [9]. Spectrofluorimetric methods determination of acrivastine in spiked human urine and pharmaceuticals [10,11].
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Development and validation of liquid chromatography tandem mass spectrometer method for the estimation of acrivastine in human plasma
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Quantification of antihistamine acrivastine in plasma by solid-phase extraction and high-performance liquid chromatography

Abstract

Introduction

Section snippets

Chemicals

Optimization of SPE procedure

Conclusion

Acknowledgements

J. Pharm. Biomed. Anal.

J. Chromatogr.

J. Pharm. Biomed. Anal.

J. Chromatogr. A

J. Pharm. Biomed. Anal.

J. Pharm. Biomed. Anal.

Arch. Pathol. Lab. Med.

Br. Med. J.