Subnanogram Quantitation of Chlorpheniramine in Plasma by a New Radioimmunoassay and Comparison With a Liquid Chromatographic Method

Antihistamines are a class of drugs that inhibit the action of histamine and are used to alleviate symptoms associated with allergic reactions, but some of them can cause side effects, the most unpleasant and dangerous of which are the sedative effects that may hinder important psychological functions and impair skilled performance. These side effects could decrease safety in certain common and critical tasks, such as driving or operating machinery, leading to accidents. Antihistamines can also cause intoxications, sometimes lethal, especially when co-administered with alcohol or other sedative drugs. Thus, the development of analytical methods for their determination in biological fluids is considered to be useful for the investigation of clinical and forensic cases. These methodologies could also be used for pharmacokinetic studies. Several liquid and a few gas chromatographic methods have been developed for the determination of antihistamines in biological matrices after proper pretreatment procedures. This article reviews the published analytical methodologies that were gathered through the search in PubMed database and the recent developments on isolation or determination of antihistamines in biological materials. Current trends and future perspectives on bioanalysis of antihistamines are also discussed. Copyright © 2016 John Wiley & Sons, Ltd.

Section: Analytical Methods For the Determination Of Antihistamines Imentioning

confidence: 99%

“…In this method, 17% cross‐reactivity of the active N‐ demethyl metabolite was also observed. This RIA method was also compared with an HPLC method and showed a lower LOD (Midha et al , ).…”

Section: Analytical Methods For the Determination Of Antihistamines Imentioning

confidence: 99%

Bioanalysis of antihistamines for clinical or forensic purposes

Katselou

Papoutsis

Νικολάου

et al. 2016

“…Chlorpheniramine and pseudoephedrine are commonly combined in one preparation for symptomatic treatment of coughs and the common cold (Yacobi et al, 1980). Some procedures have been described for the assay of either chlorpheniramine or pseudoephedrine in biological fluids, such as GC (Smith et al, 1978), HPLC with radioimmunoassay (Midha et al, 1984), fluorescence (Miyamoto, 1987) or UV (Guo et al, 1999;Bui et al, 2000;Macek et al, 2002) detections. Recently, a liquid chromatographic-tandem mass spectrometric (LC-MS-MS) method (Celma et al, 2000) and a liquid chromatographic-single quadrupole mass spectrometric (LC-MS) method (Takagaki et al, 2002) were reported to determine chlorpheniramine in human plasma.…”

Section: Introductionmentioning

confidence: 99%

Simultaneous determination of chlorpheniramine and pseudoephedrine in human plasma by liquid chromatography–tandem mass spectrometry

Chen

Zhang

Zhong

2004

A sensitive and specific procedure for simultaneous quantitation of chlorpheniramine and pseudoephedrine in human plasma has been developed and validated. Analytes were extracted from plasma samples by liquid-liquid extraction, separated on a Diamonsil C18 column (250 x 4.6 mm i.d.) and detected by tandem mass spectrometry with an atmospheric pressure chemical ionization interface. Diphenhydramine was used as the internal standard. The method has a lower limit of quantitation of 0.2 and 2.0 ng/mL for chlorpheniramine and pseudoephedrine, respectively. The intra- and inter-day relative standard deviation, calculated from quality control (QC) samples were below 4.3% for chlorpheniramine and below 9.5% for pseudoephedrine. The inter-day relative error as determined from QC samples was within 4.7% for each analyte. The overall extraction recoveries of chlorpheniramine and pseudoephedrine were 77 and 61% on average, respectively. The method was successfully applied to pharmaockinetic study of chlorpheniramine and pseudoephedrine in volunteers receiving formulations containing 4 mg of chlorpheniramine maleate and 60 mg of pseudoephedrine hydrochloride.

“…For more complex biological samples such as blood, plasma, urine and serum, a number of protocols have been reported using GC–UV (Bruce et al, 1968; Chao et al, 1991; Kabasakalian et al, 1968) or HPLC–UV (Athanikar et al, 1979; Simons et al, 1982; Westerlund & Erixson, 1979) but the bioanalytical sample preparation protocols often require a large sample size (1 ml) to measure brompheniramine levels down to 2 ng/ml and longer run times to achieve sufficient chromatographic separation. The bioanalytical procedures developed with radioimmunoassay (Midha et al, 1984), GC–MS (Maurer & Pfleger, 1988), HPLC–chemiluminescence detection (Holeman & Danielson, 1994) or GC/nitrogen–phosphorus detection (Boland et al, 2003) were both sensitive and specific. However, these methods require time consuming derivatization procedures which has limited their use for bioanalytical applications.…”

Section: Introductionmentioning

confidence: 99%

Bioavailability assessment of a brompheniramine taste‐masked pediatric formulation in a juvenile porcine model

Wang,

Shakleya,

Giacoia

et al. 2024

A brompheniramine taste‐masked pediatric formulation was developed as part of the National Institutes of Health Pediatric Formulation Initiative to help address low patient compliance caused by the bitter taste of many adult formulations. To confirm that the taste‐masked formulation can provide a similar pharmacological effect to the previous marketed adult formulations, a juvenile porcine model was used to screen the model pediatric formulation to compare the bioavailability between the marketed brompheniramine maleate and the taste‐masked maleate/tannate formulation. Pigs were dosed orally with both formulations and blood samples were obtained from 0 to 48 h. Plasma samples were prepared and extracted using solid‐phase extraction. The mass spectrometer was operated under selected ion monitoring mode. The selected ion monitoring channels were set to m/z 319.1 for brompheniramine and m/z 275.2 for the internal standard chlorpheniramine. Calibration curves were linear over the analytical range 0.2–20 ng/ml (r2 > 0.995) for brompheniramine in plasma. The intra‐ and inter‐day accuracies were between 98.0 and 105% with 5.73% RSD precision. The bioanalytical method was successfully applied to a preclinical bioavailability study. The bioavailability profiles were not significantly different between the two formulations, which demonstrates that taste‐masking with tannic acid is a promising approach for formulation modification for pediatric patients.