Tuning protonation states of tripelennamine antihistamines by cucurbit[7]uril

The formation of host–guest complexes of cucurbit[7]uril (CB7) with the antihistamine drug tripelennamine (TRP) was studied by optical and NMR spectroscopy. The experimental and computational results are consistent with inclusion of a single TRP molecule in CB7. Addition of CB7 has tuned drug protonation states associated with (de)protonation of the ethyldimethylammonium and exocyclic nitrogens with an increase in the associated pK_a values by 1.5 and 2.5 units, respectively. The incorporation of antihistamines drugs such as TRP in cucurbiturils could be utilized for switching their capability for selective binding to histamine H₁‐receptors, in the future. Copyright © 2015 John Wiley & Sons, Ltd.     

Precolumn fluorescence labeling method for simultaneous determination of hydroxyzine and cetirizine in human serum

A highly selective and sensitive method was developed for simultaneous determination of the antihistaminic drug hydroxyzine (HZ) and its pharmacologically active metabolite cetirizine (CZ) in human serum using haloperidol as internal standard. The method was based on fluorescence labeling of both drugs with a fluorescent arylboronic acid 4-(4,5-diphenyl-1H-imidazol-2-yl)phenyl boronic acid followed by separation on silica column using a mobile phase consisting of acetonitrile and water (90:10, v/v%) containing triethylamine and acetic acid. The labeling reaction conditions were optimized and the liquid-liquid extraction method was successfully applied to extract the both drugs from serum. The linearity range was 0.025-2.00 microg/mL for HZ and CZ. The limit of detection (S/N = 3) was 10 and 5 ng/mL for HZ and CZ, respectively.     

Structure elucidation of fluorescent H1 antihistamines by ultraviolet resonance Raman spectroscopy: solvent structures of tripelennamine and mepyramine

Ultraviolet Resonance Raman (UVRR) spectroscopy—a Raman technique that combines high sensitivity with high selectivity and does not suffer from background fluorescence—is applied to the fluorescent H₁ antihistamines tripelennamine (TRP) and mepyramine (MEP) in aqueous solution to elucidate their molecular structure as a function of pH. In a previous investigation of these compounds (C. Tardioli, G. Gooijer G. van der Zwan, J. Phys. Chem. B, 113 , (2009), 6949), the presence of gauche conformers caused by intramolecular interaction of the protonated alkylamine tail with the pyridine nitrogen was assumed to explain the pH dependence of the fluorescence properties. In order to validate this assumption, use is made of the resonant excitation of the aminopyridine chromophore in TRP and MEP. In that way, structural information associated with the vibrations of that moiety can be obtained, and the changes it undergoes upon protonation can be monitored. Assignment of the vibrations was achieved with the help of a number of other compounds, and quantum chemical calculations. N,N‐Dimethylaminopyridine (2DMP) and its mono‐protonated form (2DMPH⁺) were investigated, since this molecule was shown to have optical properties closely resembling those of the aminopyridine moiety in TRP and MEP. Assignment of the vibrations of 2DMP was accomplished by comparison with the resonance Raman spectra of two other reference structures, 2‐aminopyridine and dimethylaniline—for which ordinary Raman data are available—and by Gaussian calculations. UVRR spectra of TRP and MEP could be readily interpreted on the basis of vibrational assignments of the parent chromophores, i.e. 2DMP and 2DMPH⁺. Vibrations of the aminopyridine chromophore in TRP and MEP at neutral pH, where the aminoalkyl chain is protonated, are modified when compared to the vibrational pattern recorded for a fully neutral molecule in alkaline solution. This implies an electronic redistribution in the ring originating from internal hydrogen bonding between the aminoalkyl tail and the aminopyridine chromophore. Copyright © 2010 John Wiley & Sons, Ltd.     

Thin layer chromatography–densitometric determination of some non‐sedating antihistamines in combination with pseudoephedrine or acetaminophen in synthetic mixtures and in pharmaceutical formulations

The combination of certain non‐sedating antihistamines (NSA) such as fexofenadine (FXD), ketotifen (KET) and loratadine (LOR) with pseudoephedrine (PSE) or acetaminophen (ACE) is widely used in the treatment of allergic rhinitis, conjunctivitis and chronic urticaria. A rapid, simple, selective and precise densitometric method was developed and validated for simultaneous estimation of six synthetic binary mixtures and their pharmaceutical dosage forms. The method employed thin layer chromatography aluminum plates precoated with silica gel G 60 F₂₅₄ as the stationary phase. The mobile phases chosen for development gave compact bands for the mixtures FXD–PSE (I), KET–PSE (II), LOR–PSE (III), FXD–ACE (IV), KET–ACE (V) and LOR–ACE (VI) [Retardation factor (R_f) values were (0.20, 0.32), (0.69, 0.34), (0.79, 0.13), (0.36, 0.70), (0.51, 0.30) and (0.76, 0.26), respectively]. Spectrodensitometric scanning integration was performed at 217, 218, 218, 233, 272 and 251 nm for the mixtures I–VI, respectively. The linear regression data for the calibration plots showed an excellent linear relationship. The method was validated for precision, accuracy, robustness and recovery. Limits of detection and quantitation were calculated. Statistical analysis proved that the method is reproducible and selective for the simultaneous estimation of these binary mixtures. Copyright © 2013 John Wiley & Sons, Ltd.     

固相萃取/高效液相色谱法测定化妆品中5种抗组胺药物残留

建立了固相萃取/高效液相色谱(SPE/HPLC)测定化妆品中5种抗组胺药物(多西拉敏、曲吡那敏、溴苯那敏、苯海拉明、氯苯沙明)残留的分析方法。试样经三氯乙酸溶液超声提取,PCX柱净化后,以甲醇-磷酸盐缓冲溶液为流动相,经C18柱分离后进行HPLC检测。5种抗组胺药物在5.0～100 mg/L范围内均呈良好的线性关系,线性系数均大于0.999。在5.0、10.0、25.0 mg/kg 3个加标水平下的平均回收率为92%～108%,相对标准偏差(RSD,n=6)为2.1%～4.2%,检出限为0.5～1.0 mg/L。该方法灵敏度高、重现性好、定量准确。     

A fully validated method for the simultaneous determination of 11 antihistamines in breast milk by gas chromatography–mass spectrometry

Antihistamines are excreted into breast milk in small amounts; however, there are no adequate published studies or data concerning their effects on newborns and safety during breastfeeding. Thus, the development of sensitive and specific methodologies for the determination of antihistamines in breast milk is critical. A simple and sensitive GC–MS method for the simultaneous determination of 11 antihistamines (diphenhydramine, orphenadrine, chlorpheniramine, dimethindene, meclozine, hydroxyzine, loratadine, desloratadine, cetirizine, rupatadine and ebastine) in breast milk was developed and validated. The antihistamines were solid‐phase extracted and derivatized with acetic anhydride and n‐propanol. Diazepam‐d₅, hydroxyzine‐d₄ and cetirizine‐d₈ were used as internal standards. Absolute recovery values for all analytes ranged from 70.5 to 120.0%, while the limits of detection and quantification for all analytes were 1.50 and 5.00 ng/mL, respectively. All calibration curves were linear (R² ≥ 0.990) within the range 5.00–1000.0 ng/mL. Accuracy (E_r) ranged between −7.6 and 7.0%, while precision (RSD) was <12% for all antihistamines. The developed method is suitable for the investigation of antihistamine‐related clinical cases, as well as for pharmacokinetic and breastfeeding safety studies.