Novel HPTLC method for simultaneous estimation from ternary mixture of chlorpheniramine maleate, dextromethorphan hydrobromide and phenylephrine hydrochloride in syrup formulations.

OBJECTIVES: A synergic antihistamine, cough suppressant, and decongestant combination of chlorpheniramine, dextromethorphan, and phenylephrine is used to treat acute respiratory infections caused by seasonal viruses. The effective qualitative and quantitative methods require the simultaneous measurement of a ternary combination in the pharmaceutical syrup dosage form. Therefore, a new, simple, fast and robust high performance thin layer chromatographic (HPTLC) method has been developed and validated for chlorpheniramine maleate (CPM), dextromethorphan hydrobromide (DEXO) and phenylephrine hydrochloride (PE). MATERIAL AND METHODS: The chromatographic separation was carried out on precoated aluminium plates with silica gel 60 F254 as the stationary phase. Mobile phase used was chloroform: methanol: ammonia (2.5:7.5:0.3, v/v/v) for proper separation. The detection was carried out at 270nm wavelength in absorbance mode. Developed method was validated as per International Council for Harmonization (ICH) Q2 (R1) guideline. RESULTS: The linearity range is 400 to 1400ng/band for CPM, 3000 to 11500ng/band for DEXO and 1000 to 3500ng/band for PE with correlation coefficient ≥ 0.995. The consistent lower values of relative standard deviation (RSD, %) for precision and robustness study indicate the method reliability. The percent recovery ranged from 97.82 to 102.03% indicates the good accuracy of the method. CONCLUSION: The proposed method was complying for the analytical method validation parameters suggested by the ICH Q2 (R1) guideline. The method was found to be simple, rapid and reliable for the simultaneous estimation of CPM, DEXO and PE from its pharmaceutical syrup dosage form. The method was successfully applied to quantify these analytes from the several pharmaceutical syrup dosage form.

Development of an improved method to estimate the days of continuous drug ingestion, based on the micro-segmental hair analysis.

To prove drug-related crimes, it is important to estimate the date on which a specific drug was ingested. Previously, we developed a method, "micro-segmental hair analysis," to estimate the day of ingestion of a single-dose drug by segmenting a hair strand into 0.4-mm segments, which correspond to daily hair growth. In this study, the method was improved to estimate the days of continuous drug ingestion. The subjects ingested four hay-fever medicines (fexofenadine, epinastine, cetirizine, and loratadine) continuously (1-18 days) and chlorpheniramine as a single dose at intervals of several weeks as an internal temporal marker (ITM). The hair strands of the subjects were collected and subjected to a micro-segmental analysis. The distribution curves of each hay-fever medicine in a hair strand had broad peaks reflecting the number of days of drug ingestion. The positions on the curves corresponding to the first and final ingestion days of hay-fever medicines were identified using the ITM. The positions were near the hair segments on both ends of full width at half maximum (W2 ) of the broad peak. When the first and final days of continuous ingestion were estimated using W2 , independent of peak shape, the absolute average error from the actual ingestion days was approximately 2 days. Overall, we established a method to estimate the days of both single-dose and continuous drug ingestions. Furthermore, the method would be useful to investigate drug ingestion history in various scenes such as drug-related crimes and therapeutic drug monitoring.

Facile electrochemical preparation of overoxidizedpolypyrrole/RGO composite for ds-DNA immobilization: a novel signal amplified sensing platform for electrochemical determination of chlorpheniramine.

BACKGROUND: Chlorpheniramine (CPA), thanks to its relatively lower side effects, is a widely prescribed medicine for alleviating allergic symptoms as well as some medical emergencies. Owning to this extensive use, many efforts have been directed to measure chlorpheniramine both in vivo and in vitro. High performance liquid chromatography (HPLC), both normal and reverse phase, as well as spectrochemical and electrochemical methods are analytical approaches which have been extensively exploited for determination of CPA. Among them, electrochemical techniques have found elegant place for analysis of CPA due to simplicity, sensitivity and ease of instrumentation. METHODS: Herein, we have reported the preparation and characterization of a biosensor by immobilization of double-stranded DNA on the surface of overoxidizedpolypyrrole-reduced graphene oxide modified pencil graphite electrode (ds-DNA-PPyox/RGO/PGE) as well as its novel usability in measurement of chlorpheniramine (CPA). Scanning electron microscopy (SEM), electrochemical impedance spectroscopy (EIS), UV-Vis spectroscopy and differential pulse voltammetry (DPV) were exploited in order to characterize and evaluate the performance of the proposed biosensor. RESULTS: Final results showed that proposed strategy for modification of PGE introduces an ultra-sensitive biosensor for CPA which offers the best detection limitamong all previously reported electrochemical sensors for CPA. Taking advantage of this biosensor for determination of CPA, a wide linear dynamic range from 0.05 to 200 µM, and a low limit of detection 0.023 µM were obtained by using DPV method. Usability of this biosensor was also confirmed by determination of CPA in tablet and spiked urine samples. CONCLUSIONS: Overoxidized polypyrrole-reduced graphene oxide offered a suitable substrate for immobilization of ds-DNA by which a new biosensor for determination of CPA was fabricated. Proposed biosensor can successfully be used for determination of CPA in urine samples taking advantage of electroanalytical methods. Graphical abstract.

Enantiomeric Separation of Meclizine Hydrochloride in Pharmaceutical Dosage Form by HPLC Method.

OBJECTIVE: A basic, powerful and isocratic chiral fluid chromatographic technique was created and approved for the enantiomeric partition of meclizine hydrochloride in pharmaceutical dose structure. METHODS: The chromatographic partition was accomplished on Phenomenex® Lux Cellulose 1 (250 mm x 4.6 mm i.d, 5 µm molecule size) section utilizing portable stage framework containing acetonitrile: 25mM ammonium bicarbonate (75:25%v /v). The versatile stage was siphoned on the segment at the stream pace of 1.0 mL/min, and UV recognition was done at 230 nm. RESULT: The breaking points of recognition and measurement were observed to be 0.25 µg/mL and 1.00 µg/mL individually, for 20µL infusion volume. The alignment bend demonstrated phenomenal linearity over the focus scope of 1-5 µg/mL for (±) meclizine enantiomers with a relationship coefficient (r2 = 0.999). The recuperation investigation of meclizine from tablet plan was observed to be 97.33% and 98.81% separately. Meclizine standard arrangement and versatile stage were observed to be steady for in any event 32h. The meclizine enantiomers were very much settled with mean maintenance times of about (+) Meclizine at 13.14 min and (-) Meclizine at 14.33 min individually. CONCLUSION: The created technique was broadly approved and demonstrated to be hearty, exact, exact and appropriate for the examination of meclizine enantiomers in tablet measurement structure and security investigations of meclizine.

High-speed imaging reveals how antihistamine exposure affects escape behaviours in aquatic insect prey.

Aquatic systems receive a wide range of pharmaceuticals that may have adverse impacts on aquatic wildlife. Among these pharmaceuticals, antihistamines are commonly found, and these substances have the potential to influence the physiology of aquatic invertebrates. Previous studies have focused on how antihistamines may affect behaviours of aquatic invertebrates, but these studies probably do not capture the full consequences of antihistamine exposure, as traditional recording techniques do not capture important animal movements occurring at the scale of milliseconds, such as prey escape responses. In this study, we investigated if antihistamine exposure can impact escape responses in aquatic insect, by exposing damselfly (Coenagrion hastulatum) larvae to two environmentally relevant concentrations (0.1 and 1 µg L-1) of diphenhydramine. Importantly, we used a high-speed imaging approach that with high-time resolution captures details of escape responses and, thus, potential impacts of diphenhydramine on these behaviours. Our results show overall weak effects of antihistamine exposure on the escape behaviours of damselfly larvae. However, at stage 2 of the C-escape response, we found a significant increase in turning angle, which corresponds to a reduced swimming velocity, indicating a reduced success at evading a predator attack. Thus, we show that low concentrations of an antihistamine may affect behaviours strongly related to fitness of aquatic insect prey - effects that would have been overlooked using traditional recording techniques. Hence, to understand the full consequences of pharmaceutical contamination on aquatic wildlife, high-speed imaging should be incorporated into future environmental risk assessments.

[Detection of Physiological Activity of Pharmaceuticals in Wastewater and River Water].

　Pharmaceuticals are widely found in aquatic environments worldwide. Concern about their potential risks to aquatic species has been raised because they are designed to be biologically active. To address this concern, we must know whether biological activity of pharmaceuticals can be detected in waters. Nearly half of all marketed pharmaceuticals act by binding to the G protein-coupled receptor (GPCR). In this study, we measured the physiological activity of GPCR-acting pharmaceuticals in effluent from a wastewater treatment plant (WWTP) and upstream and downstream of its outfall in Japan during 2 years. We used the in vitro transforming growth factor-α (TGFα) shedding assay, which accurately and sensitively detects GPCR activation, to investigate the antagonistic activities of water extracts against receptors for dopamine (D2) and histamine (H1). Activities detected in waters were quantified as antagonist equivalent quantities (EQs). In WWTP effluent extracts, antagonistic activity was detected at several hundred ng/L of sulpiride-EQ (D2) and several µg/L of diphenhydramine (DIP)-EQ (H1). In downstream river water extracts, antagonistic activity against H1 was around several hundred ng/L of DIP-EQ, higher than that upstream owing to the WWTP effluent. This review discusses the research needed to resolve the concern about potential risks of pharmaceuticals in waters to aquatic species.

IDENTIFICATION AND DETERMINATION OF RUPATADINE AND FEXOFENADINE BY DENSITOMETRIC METHOD.

Simple, precise and accurate densitometric methods were developed for the determination of two antihistamine drugs. rupatadine and fexofenadine. Silica gel 60 F254 HPTLC plates were used as stationary phase, while mixtures of acetonitrile - water - 25% ammonia (90 : 10 : 1, v/v/v) and acetonitrile - methanol -acetate buffer at pH 5.5 (3 : 2 : 5, v/v/v) were used as mobile phases for rupatadine and fexofenadine, respectively. The detection of rupatadine and fexofenadine was conducted out at 256 and 210 nm, respectively. The limit of detection and the limit of quantification for rupatadine were found to be 0.3 and 0.1 µg/spot, respectively, and for fexofenadine, 5 and 2 µg/spot, respectively.

Corticosteroid adulteration in proprietary Chinese medicines: a recurring problem.

OBJECTIVES: To investigate adulteration of proprietary Chinese medicines with corticosteroids in Hong Kong. DESIGN: Case series with cross-sectional analysis. SETTING: A tertiary clinical toxicology laboratory in Hong Kong. PATIENTS: All patients using proprietary Chinese medicines adulterated with corticosteroids and referred to the authors' centre from 1 January 2008 to 31 December 2012. MAIN OUTCOME MEASURES: Patients' demographic data, clinical presentation, medical history, drug history, laboratory investigations, and analytical findings of the proprietary Chinese medicines were analysed. RESULTS: The records of 61 patients who consumed corticosteroid-adulterated proprietary Chinese medicines were reviewed. The most common corticosteroid implicated was dexamethasone. Co-adulterants such as non-steroidal anti-inflammatory drugs and histamine H1-receptor antagonists were detected in the proprietary Chinese medicine specimens. Among the patients, seven (11.5%) required intensive care, two (3.3%) died within 30 days of presentation, and 38 (62.3%) had one or more complications that were potentially attributable to exogenous corticosteroids. Of 22 (36.1%) patients who had provocative adrenal function testing performed, 17 (77.3% of those tested) had adrenal insufficiency. CONCLUSION: The present case series is the largest series of patients taking proprietary Chinese medicines adulterated with corticosteroids. Patients taking these illicit products are at risk of severe adverse effects, including potentially fatal complications. Adrenal insufficiency was very common in this series of patients. Assessment of adrenal function in these patients, however, has been inadequate and routine rather than discretionary testing of adrenal function is indicated in this group of patients. The continuing emergence of proprietary Chinese medicines adulterated with western medication indicates a persistent threat to public health.

Development of normalized spectra manipulating spectrophotometric methods for simultaneous determination of Dimenhydrinate and Cinnarizine binary mixture.

Simultaneous determination of Dimenhydrinate (DIM) and Cinnarizine (CIN) binary mixture with simple procedures were applied. Three ratio manipulating spectrophotometric methods were proposed. Normalized spectrum was utilized as a divisor for simultaneous determination of both drugs with minimum manipulation steps. The proposed methods were simultaneous constant center (SCC), simultaneous derivative ratio spectrophotometry (S(1)DD) and ratio H-point standard addition method (RHPSAM). Peak amplitudes at isoabsorptive point in ratio spectra were measured for determination of total concentrations of DIM and CIN. For subsequent determination of DIM concentration, difference between peak amplitudes at 250 nm and 267 nm were used in SCC. While the peak amplitude at 275 nm of the first derivative ratio spectra were used in S(1)DD; then subtraction of DIM concentration from the total one provided the CIN concentration. The last RHPSAM was a dual wavelength method in which two calibrations were plotted at 220 nm and 230 nm. The coordinates of intersection point between the two calibration lines were corresponding to DIM and CIN concentrations. The proposed methods were successfully applied for combined dosage form analysis, Moreover statistical comparison between the proposed and reported spectrophotometric methods was applied.

Evaluating the efficiency of spectral resolution of univariate methods manipulating ratio spectra and comparing to multivariate methods: an application to ternary mixture in common cold preparation.

Simple, accurate, and selective methods have been developed and validated for simultaneous determination of a ternary mixture of Chlorpheniramine maleate (CPM), Pseudoephedrine HCl (PSE) and Ibuprofen (IBF), in tablet dosage form. Four univariate methods manipulating ratio spectra were applied, method A is the double divisor-ratio difference spectrophotometric method (DD-RD). Method B is double divisor-derivative ratio spectrophotometric method (DD-RD). Method C is derivative ratio spectrum-zero crossing method (DRZC), while method D is mean centering of ratio spectra (MCR). Two multivariate methods were also developed and validated, methods E and F are Principal Component Regression (PCR) and Partial Least Squares (PLSs). The proposed methods have the advantage of simultaneous determination of the mentioned drugs without prior separation steps. They were successfully applied to laboratory-prepared mixtures and to commercial pharmaceutical preparation without any interference from additives. The proposed methods were validated according to the ICH guidelines. The obtained results were statistically compared with the official methods where no significant difference was observed regarding both accuracy and precision.

Fast determination of diphenhydramine hydrochloride in reconstitutable syrups by CWT, PLS AND PCR methods.

Diphenhydramine hydrochloride (DPH), a histamine H1-receptor antagonist, is widely used as antiallergic, antiemetic and antitussive drug found in many pharmaceutical preparations. In this study, a new reconstitutable syrup formulation of DPH was prepared because it is more stable in solid form than that in liquid form. The quantitative estimation of the DPH content of a reconstitutable syrup formulation in the presence of pharmaceutical excipients, D-sorbitol, sodium citrate, sodium benzoate and sodium EDTA is not possible by the direct absorbance measurement. Therefore, a signal processing approach based on continuous wavelet transform was used to determine the DPH in the reconstitutable syrup formulations and to eliminate the effect of excipients on the analysis. The absorption spectra of DPH in the range of 5.0-40.0 µg/mL were recorded between 200-300 nm. Various wavelet families were tested and Biorthogonal1.1 continuous wavelet transform (BIOR1.1-CWT) was found to be optimal signal processing family to get fast and desirable determination results and to overcome excipient interference effects. For a comparison of the experimental results obtained by partial least squares (PLS) and principal component regression (PCR) methods were applied to the quantitative prediction of DPH in the mentioned samples. The validity of the proposed BIOR1.1-CWT, PLS and PCR methods were achieved analyzing the prepared samples containing the mentioned excipients and using standard addition technique. It was observed that the proposed graphical and numerical approaches are suitable for the quantitative analysis of DPH in samples including excipients.

Post-mortem evidence of doxylamine in toxicological analyses.

BACKGROUND: Doxylamine (DA) is widely available in pharmacies without prescription and can be used in suicidal intention because of its sedative and anticholinergic properties. Research of literature shows that only a few publications deal with post-mortem evidence of DA and its interpretation during toxicological examination. MATERIAL AND METHODS: In this study, all cases with a positive detection of DA during toxicological analyses with high-performance liquid chromatography in the time period 2000 to 2010 at the Institute of Legal Medicine and Forensic Sciences in Berlin, Germany were retrospectively analysed and interpreted, taking into account police investigations, autopsy results and toxicological analyses. RESULTS: In total, 22 cases with DA intoxications were discovered (♂=16/♀=6, age-at-death range 17 to 90years). Maximum blood concentration was measured at 77.5µg/mL. Cause of death was due to DA intoxication in eight suicide cases; seven of those were combined intoxications (DA and other substances, particularly diphenhydramine). During the evaluated time period no monointoxications with DA were discovered. CONCLUSION: Benchmarks published in past literature are meant as orientation during evaluation of post-mortem DA evidence. These should not be used as absolute values and need to be interpreted individually in each case. Post-mortem redistribution needs to be considered as a main factor in alteration of DA concentration measurement. Furthermore, proof of DA ingestion found in gastric content should only be interpreted quantitatively due to unreliable calculation of the ingested amount. In conclusion, a variety of factors, such as the time period between time of death and the time of the first toxicological analysis, the condition of the body and the findings at autopsy, must also be critically considered.

Utility of 4-chloro-7-nitrobenzofurazan (NBD-CI) for the Spectrophotometric and spectrofluorometric determination of several antihistamine and antihypertensive drugs.

New, sensitive, and selective spectrophotometric and spectrofluorometric methods have been developed for determination of clemastine hydrogen fumarate (Clem), loratadine (Lor), losartan potassium (Los), and ramipril (Ram) in both pure form and pharmaceutical formulations using 4-chloro-7-nitrobenzofurazan (NBD-CI), which is a highly sensitive chromogenic and fluorogenic reagent. The relation between absorbance at 470, 467, 471, and 469 nm and the concentration was linear over the ranges 5-35, 10-100, 10-90, and 10-120 microg/mL for Clem, Lor, Los, and Ram, respectively. The complexation products were also measured spectrofluorometrically at the emission wavelength 535 nm for Clem, Lor, and Ram and at 538 nm for Los with excitation at 477 and 452 nm for Clem and Lor, respectively, and 460 nm for both Los and Ram. The fluorescence intensity was directly proportional to the drug concentration over the ranges 0.05-0.5, 5-20, 1-6, and 2-15 microg/mL for Clem, Lor, Los, and Ram, respectively. The methods were successfully applied for the determination of the studied drugs in pharmaceutical dosage forms with excellent recovery.

Hydroxyzine distribution in postmortem cases and potential for redistribution.

Hydroxyzine is an antihistaminic with sedative properties used in the control of anxiety and emesis. Peripheral blood hydroxyzine concentrations are compared to central blood and liver concentrations in 10 medical examiner cases. Specimens were initially screened for alcohol and simple volatiles by GC-FID headspace analysis, ELISA for drugs of abuse, and alkaline drugs by GC/MS. Hydroxyzine, when detected by the alkaline drug screen, was subsequently confirmed and quantified by a specific GC-NPD procedure. Data suggest that postmortem peripheral blood hydroxyzine concentrations may be considered therapeutic to at least 0.24 mg/L and corresponding liver concentrations to at least 4.9 mg/kg. Hydroxyzine concentrations ranged 0.07-3.0mg/L in peripheral blood, 0.04-3.8 mg/L in central blood, and 0.88-55 mg/kg in liver. Hydroxyzine central blood to peripheral blood ratios averaged 0.92±0.25 (±standard deviation; N=6). Liver to peripheral blood ratios, on the other hand, were higher and averaged 13.8±6.2 (±standard deviation; N=10). Given that a liver to peripheral blood ratio less than 5 is consistent with little to no postmortem redistribution while exceeding 20-30 is indicative of propensity for significant postmortem redistribution, these data suggest that hydroxyzine is prone to a moderate degree of postmortem redistribution.

Using an innovative Quality-by-Design approach for development of a stability indicating UHPLC method for ebastine in the API and pharmaceutical formulations.

A stability-indicating ultra high performance liquid chromatographic (UHPLC) method has been developed for purity testing of ebastine and its pharmaceutical formulations. Successful chromatographic separation of the API from impurities was achieved on a Waters Acquity UPLC BEH C18, 50 mm × 2.1 mm, 1.7 µm particle size column with gradient elution of 10 mM acetate buffer pH 6.2 and a mixture of acetonitrile/2-propanol (1:1) as the mobile phase. Incorporating Quality by Design (QbD) principles to the method development approach by using the chromatography modeling software DryLab4 allows the visualization of a "Design Space", a region in which changes to method parameters will not significantly affect the results as defined in the ICH guideline Q8 (R2). A verification study demonstrated that the established model for Design Space is accurate with a relative error of prediction of only 0.6%. The method was fully validated for specificity, linearity, accuracy and precision, and robustness in compliance to the ICH guideline Q2 (R1). The method was found to be linear in the concentration range from the quantification limit (LOQ) to 125% of the specification limit for ebastine and each of the impurities with correlation coefficients of not less than 0.999. The recovery rate was between 98.15 and 100.30% for each impurity. The repeatability and intermediate precision (RSD) were less than 3.2% for ebastine and each of the impurities. The robustness of the developed method was studied by varying the six parameters: gradient time, temperature, ternary composition of the eluent, flow rate and start and end concentration of the gradient at 3 levels (+1, 0, -1). The resulting 729 experiments were performed in silico from the previously constructed model for Design Space and showed that the required resolution of 2.0 can be reached in all experiments. To prove the stability-indicating performance of the method, forced degradation (acid and base hydrolysis, oxidation, photolytic and thermal stress conditions) of ebastine was carried out. Baseline separation could be achieved for all peaks of the impurities, the degradation products and the API. Total run time was only 4 min, which is an impressive 40-fold increase in productivity in comparison to the method published in the Ph. Eur. monograph and allowed purity testing of more than 360 samples per day.

Single and mixed chemically modified carbon paste ion-selective electrodes for determination of ketotifen fumarate.

New modified carbon paste electrodes for determination of ketotifen fumarate in its pure and pharmaceutical preparations were constructed. The used modifiers are ketotifen phosphotungestate (Keto(3) PT), and ketotifen tetraphenylborate (Keto-TPB). Single and mixed ion-associate electrodes were prepared. Both Keto-TPB and mixed (Keto-TPB and Keto(3) PT) electrodes have a linearity range of 1.00 × 10(-5) -1.00 × 10(-2) mol L(-1) . The slopes were 58.30 and 54.20 mV/decade for Keto-TPB and mixed chemically modified carbon paste electrodes (CMCPE), respectively. The limits of detection were 1.42 × 10(-6) and 1.00 × 10(-5) mol L(-1) for Keto-TPB and mixed CMCPEs, respectively. The potential variation due to pH change is considered acceptable in the pH ranges 4.44-9.11 and 2.50-9.00 for Keto-TPB and mixed ion-exchanger CMCPE, respectively. The response time was ≤10 s for both electrodes. Selectivity coefficients values towards different inorganic cations, sugars, and amino acids reflect high selectivity of the prepared electrodes. Potentiometric titrations and standard addition methods were applied for the determination of ketotifen ion in its pure samples and pharmaceutical formulations (Zaditen tablet and syrup) using proposed electrodes. The electrodes were also tested in flow injection analysis (FIA). The results obtained from both methods were statistically treated by F- and t-tests. The carbon paste electrodes have the advantages of being more easily prepared and longer life span compared to the plastic membrane electrodes previously reported.

Identification and determination of ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method.

Conditions for determination of: ketotifen hydrogen fumarate, azelastine hydrochloride, dimetindene maleate and promethazine hydrochloride by densitometric method in substances and pharmaceuticals were provided. Maximum wavelenghts were: 228 nm for ketotifen hydrogen fumarate, 295 nm for azelastine hydrochloride, 265 nm for dimetindene maleate and 255 nm for promethazine hydrochloride. The limits of quantification were in the ranges of 0.2-5 microg/spot. The statistical data showed adequate accuracy and precision of developed methods.

The antihistamine diphenhydramine is extremely persistent in agricultural soil.

The widely used antihistamine diphenhydramine is present in municipal biosolids, and is detected in runoff from agricultural land fertilized with biosolids. In the present study the kinetics and major pathways of diphenhydramine dissipation in a loam, sandy loam, and clay loam soil were determined in laboratory incubations. The time to dissipate 50% (DT(50)) of (14)C-diphenhydramine residues at 30 °C ranged from 88 ± 28 days in the clay loam to 335 ± 145 days in the loam soil. Mineralization of (14)C was insignificant, and diphenhydramine-N-oxide was the only detected extractable transformation product elucidated by radioisotope and HPLC-MS methods. There were no significant effects of municipal biosolids on the kinetics or pathways of removal. Overall, diphenhydramine is quite persistent in soils, and formation of non-extractable soil-bound residues is the major mechanism of diphenhydramine dissipation.

Validated spectroflurimetric determination of some H1 receptor antagonist drugs in pharmaceutical preparations through charge transfer complexation.

A validated simple, rapid, and selective spectrofluorimetric method was developed for the determination of some antihistaminic H(1) receptor antagonist drugs namely ebastine (EBS), cetirizine dihydrochloride (CTZ), and fexofenadine hydrochloride (FXD). The method is based on the reaction of the cited drugs with some Π acceptors namely p-chloranilic acid (CLA), tetracyanoethylene (TCNE), and 2,3-dichloro-5,6-dicyano-p-benzoquinone (DDQ) to give highly fluorescent derivatives. The fluorescence intensity-concentration plots were rectilinear over the concentration ranges of 0.2-3.0, 0.2-2.5 and 0.15-2.0 µg/ml for EBS with CLA, DDQ, and TCNE respectively; 0.5-7.0, 0.5-6.0, and 0.2-4.0 µg/ml for CTZ with the previously mentioned reagents, and 0.2-3.5, 0.5-6.0, and 0.2-3.5 µg/ml for FXD. The factors affecting the formation of the reaction products were carefully studied and optimized. The method was applied for the determination of the studied drugs in their dosage forms. The results obtained were in good agreement with those obtained by the comparison methods. Reactions Stoichiometries of the complexes formed between the studied drugs and Π acceptors were defined by the Job's method of the continuous variation and found in 1:1 in all cases.

In vitro antibacterial activity of some antihistaminics belonging to different groups against multi-drug resistant clinical isolates

Antihistaminics are widely used for various indications during microbial infection. Hence, this paper investigates the antimicrobial activities of 10 antihistaminics belonging to both old and new generations using multiresistant Gram-positive and Gram-negative clinical isolates. The bacteriostatic activity of antihistaminics was investigated by determining their MIC both by broth and agar dilution techniques against 29 bacterial strains. Azelastine, cyproheptadine, mequitazine and promethazine were the most active among the tested drugs. Diphenhydramine and cetirizine possessed weaker activity whereas doxylamine, fexofenadine and loratadine were inactive even at the highest tested concentration (1 mg/ml). The MIC of meclozine could not be determined as it precipitated with the used culture media. The MBC values of antihistaminics were almost identical to the corresponding MIC values. The bactericidal activity of antihistaminics was also studied by the viable count technique in sterile saline solution. Evident killing effects were exerted by mequitazine, meclozine, azelastine and cyproheptadine. Moreover, the dynamics of bactericidal activity of azelastine were studied by the viable count technique in nutrient broth. This activity was found to be concentration-dependant. This effect was reduced on increasing the inoculum size while it was increased on raising the pH. The post-antimicrobial effect of 100 fg/ml azelastine was also determined and reached up to 3.36 h.