Determination Of Diphenhydramine Research Articles

Validated Analytical Spectrofluorimetric Method for Quantitation of Diphenhydramine HCl in Commercial Dosage Forms

Diphenhydramine HClis a weakly fluorescent drug having tertiary amine group forming ion pair complex with eosin Y in dichloromethane at pH 5 in disodium hydrogen phosphate-citric acid buffer solution. The complex formation was the basis for the development of new analytical method for determination of active diphenhydramine in pharmaceutical formulations. The stoichiometric ratio between diphenhydramine and eosin Y was studied by mole ratio method and found to be 2:1. The ion-pair complex showed maximum fluorescence emission intensity at 554 nm with excitation at 259 nm. The linear dynamic range was obtained in the concentration range of 2-22 µg mL-1 with a linear equation of FI = 0.361 + 13.675 C. The apparent Gibb’s free energy (ΔGº) was calculated and found to be -80.783 KJ mol-1, confirmed the feasibility of the reaction. The proposed method was successfully applied to the determination of diphenhydramine HCl in pharmaceutical formulations and in good agreement with the reference method.

Simultaneous determination of ten antihistamine drugs in human plasma using pipette tip solid‐phase extraction and gas chromatography/mass spectrometry

Ten antihistamine drugs, diphenhydramine, orphenadrine, chlorpheniramine, diphenylpyraline, triprolidine, promethazine, homochlorcyclizine, cyproheptadine, cloperastine and clemastine, have been found to be extractable from human plasma samples using MonoTip C18 tips, inside which C18- bonded monolithic silica gel was fixed. Human plasma (0.1 mL) containing the ten antihistamines was mixed with 0.4 mL of distilled water and 25 microL of a 1 M potassium phosphate buffer (pH 8.0). After centrifugation of the mixture, the supernatant fraction was extracted to the C18 phase of the tip by 25 repeated aspirating/dispensing cycles using a manual micropipettor. The analytes retained on the C18 phase were then eluted with methanol by five repeated aspirating/dispensing cycles. The eluate was injected into a gas chromatography (GC) injector without evaporation and reconstitution steps, and was detected by a mass spectrometer with selected ion monitoring in the positive-ion electron impact mode. The separation of the ten drugs from each other and from impurities was generally satisfactory using a DB-1MS column (30 m x 0.32 mm i.d., film thickness 0.25 microm). The recoveries of the ten antihistamines spiked into plasma were 73.8-105%. The regression equations for the ten antihistamines showed excellent linearity with detection limits of 0.02-5.0 ng/0.1 mL. The within-day and day-to-day coefficients of variation for plasma were not greater than 9.9%. The data obtained from determination of diphenhydramine and chlorpheniramine in human plasma after oral administration of the drugs are also presented.

Simultaneous determination of diphenhydramine, itsN-oxide metabolite and their deuterium-labeled analogues in ovine plasma and urine using liquid chromatography/electrospray tandem mass spectrometry

Simultaneous determination of diphenhydramine, itsN-oxide metabolite and their deuterium-labeled analogues in ovine plasma and urine using liquid chromatography/electrospray tandem mass spectrometry

Determination of antihistamines based on the formation of mixed aggregates with surfactants.

The determination of antihistamines based on the measurement of the critical micelle concentration (c.m.c.) of mixed sodium dodecyl sulfate (SDS)-antihistamine aggregates is proposed. The dye Coomassie Brilliant Blue G (CBBG) was used as a photometric probe for the rapid determination of c.m.c.s. The micellar properties of these drugs permitted the determination of diphenhydramine, antazoline, tripelennamine, diphenylpyraline and clemizole at the micron level with detection limits ranging between 0.1 and 0.7 microns. Hence the proposed method surpassed existing alternative photometric methods used routinely in the quality control of these drugs in sensitivity and featured similar detection limits to fluorimetric methods. The relative standard deviation for 6 micron diphenhydramine was 3.7%. The method was applied to the determination of these drugs in pharmaceutical preparations (solutions, capsules, creams and pills). which were analyzed directly after dissolution of the samples in distilled water.

Fluorometric determination of diphenhydramine by flow-injection analysis

A sensitive, rapid and simple flow injection procedure for the determination of diphenhydramine has been designed based on a fluorometric approach. An aqueous solution of diphenhydramine is injected into a carrierreagent stream containing Ce(IV) in dilute sulphuric acid and the fluorescence intensity of the Ce(III) produced is monitored. Chemical, FIA and instrumental variables were optimized. Analytical features of the method are: linear range 0.2–2 ppm, precision 0.7%, sample throughput 80/h. The influence of some foreign substances which can be found in typical pharmaceutical samples containing diphenhydramine was also investigated. The diphenhydramine content of a pharmaceutical preparation was determined.

Method for the determination of diphenhydramine in rabbit whole blood by high-performance liquid chromatography (HPLC) with ultraviolet (UV) detection in conjunction with gas chromatography (GC) with mass selective detection (MSD).

An HPLC/GC-MSD method for the determination of diphenhydramine in rabbit whole blood has been developed and validated. This method is based on a liquid-liquid extraction and reversed-phase chromatography with ultraviolet absorbance detection monitored at 258 nm. HPLC eluant fractions containing diphenhydramine and the internal standard, orphenadrine, were collected, reextracted, then subjected to GC-MSD analysis. Whole blood was utilized, thereby decreasing the required sample volume and increasing the sensitivity of the assay. Diphenhydramine concentrations can be quantitated over a range of 1 to 1000 ng/ml whole blood.

Sensitive high-performance liquid chromatographic (HPLC) determination of diphenhydramine in plasma using fluorescence detection.

Sensitive high-performance liquid chromatographic (HPLC) determination of diphenhydramine in plasma using fluorescence detection.

High-performance liquid chromatography method for the determination of diphenhydramine in human plasma

High-performance liquid chromatography method for the determination of diphenhydramine in human plasma

Determination of Diphenhydramine in Rat Milk and Plasma and Its Effects on Milk Composition and Mammary Gland Nucleic Acids

To study the excretion of diphenhydramine into rat milk, milk and plasma concentrations of diphenhydramine were determined in lactating rats after single or multiple oral doses. Four hours after a single dose of 40 or 100 mg/kg of diphenhydramine, milk concentrations of the drug averaged 0.30 and 2.2 micrograms/mL, respectively, in two experiments, and the milk:plasma ratios ranged from 4.4 to 7.5. Multiple doses did not significantly affect the plasma or milk concentrations or the milk:plasma ratios, which were similar to the theoretical milk:plasma ratio based on pH partitioning for this compound (i.e., 4.0). Although the concentration of diphenhydramine was higher in milk than in plasma, the estimated dose received by the pups (0.057 mg/kg/d) based on the milk concentrations was much lower than that given to the mother. Oral diphenhydramine treatment at doses which significantly reduced maternal food consumption had no effect on milk solid, lipid, protein, or lactose concentrations, nor on mammary gland RNA or DNA content, indicating that diphenhydramine did not adversely affect lactation.

Determination of diphenhydramine in biological fluids by capillary gas chromatography using nitrogen—phosphorus detection : Application to placental transfer studies in pregnant sheep

A nitrogen—phosphorus detection—gas chromatographie method, which provides improved sensitivity and selectivity for diphenhydramine, is reported. A 25 m x 0.31 mm cross-linked, 5% phenylmethyl silicone-coated fused-silica capillary column (film thickness 0.52 μm) was used for all analyses. The splitless capillary injection mode was employed with a 2-μl sample being introduced by an automatic liquid sampler. Standard curves, using orphenadrine as an internal standard, were linear in the range 2–320 ng of diphenhydramine per 0.5 ml of sheep plasma. This represents an amount of diphenhydramine from ca. 40 pg to 6.4 ng at the detector. Chromatographic separation of diphenhydramine and orphenadrine was excellent, with no interference from endogenous plasma constituents. Applicability of the method was demonstrated by a placental transfer study in a chronically instrumented pregnant sheep following a 100 mg intravenous injection of diphenhydramine to the ewe.

Determination of diphenhydramine in photochemically decomposed solutions

For the study of the photochemical decomposition of diphenhydramine a rapid and simple method of determination is needed in which the decomposing do not interfere. It is shown that the method of separation by thin-layer chromatography followed by extraction of the diphenhydramine spot, reaction with methyl orange and sprectrophoto metric measurement of the absorbance of the complex provides reliable. Comparison of this method with a new gas Chromatographie method shows that the latter method is also satisfactory when applied to measurement of diphenhydramine in photochemically and thermochemically decomposed solutions. Two methods, which include extractions of the photochemically decomposed solution with organic solvents, do not provide reliable results compared with the results of the gas chromatographic method. One of these two methods is a proposed modification of the U.S.P. XVIII method.

Determination of Diphenhydramine and Certain Related Compounds by Ultraviolet Spectrophotometry.

Determination of Diphenhydramine and Certain Related Compounds by Ultraviolet Spectrophotometry.