Triprolidine Research Articles

Method Development for Separation of Active Ingredients in Cold Medicines by Micellar Electrokinetic Chromatography

Separation of nine commonly used active ingredients in cold medicines, were demonstrated by micellar electrokinetic chromatography. The ingredients included paracetamol, chlorpheniramine maleate, diphenhydramine hydrochloride, triprolidine hydrochloride, phenylpropanolamine hydrochloride, dextromethorphan hydrobromide, loratadine, aspirin and caffeine. Effects of buffer concentrations, pH, organic modifiers and capillary length were investigated. The optimum conditions were achieved in 10 mM sodium dihydrogenphosphate-sodium tetraborate buffer, pH 9.0, containing 50 mM sodium dodecyl sulfate and 28% v/v acetonitrile using the effective length of 50 cm, the separating voltage of +15 kV and the capillary temperature of 30°C. Separation of all peaks was obtained within 28.4 min with a resolution of 1.2.

SPECTROPHOTOMETRIC DETERMINATION OF TRIPROLIDINE HYDROCHLORIDE BY m-DINITROBENZENE IN PHARMACEUTICAL PREPARATIONS

ABSTRACT Triprolidine hydrochloride reacts with m-dinitrobenzene and sodium hydroxide to give a purple coloured complex, after heating at 60°C for 40 s having maximum absorbance at 550 nm. The reaction is selective for triprolidine hydrochloride with 0.01 mg/10 mL as visual limit of quantitation and provides a basis for a new spectrophotometric determination. The reaction obeys Beer's Law from 0.01 to 2 mg/10 mL of triprolidine hydrochloride and the relative standard deviation is 0.66%. The quantitative assessments of tolerable amounts of other drugs not interfering are also studied.

Triprolidine: 104-Week Feeding Study in Rats

Triprolidine: 104-Week Feeding Study in Rats. Greenman, D. L., Sheldon, W., Schieferstein, G., Allen, R., and Allaben, W. T. (1995). Fundam. Appl. Toxicol. 27, 223-231. The antihistamine, triprolidine hydrochloride, was fed at dietary concentrations of 0, 250, 1000, or 2000 ppm (as the free base) to groups of 60 Fischer 344 (F344) rats of each sex for up to 2 years to evaluate its potential carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and hematology, clinical chemistry, and histopathology were evaluated. A complete histopathological evaluation was performed on all other animals; survivors were killed at 2 years. Survival was significantly extended in triprolidine-treated males and females, particularly at the high dose. At the close of the study high-dose males and females had gained significantly less body weight than controls. Among rats killed at 65 weeks females in the mid- and high-dose groups weighed significantly less than controls, but weights of control and dosed males were not significantly different. The incidences of numerous lesions tended to decrease with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c-cell hyperplasia and neoplasia, mammary gland hyperplasia and fibroadenomas, and uterine stromal polyps, and in males, anterior pituitary gland adenomas, preputial gland neoplasia, thyroid c-cell hyperplasia, pancreatic islet neoplasia, mononuclear cell leukemia, and the combination of lymphocytic, histiocytic, and undifferentiated cell malignant lymphomas and mononuclear leukemia, all exhibited negative dose trends. Cytoplasmic alterations of the parotid gland and numerous liver lesions tended to be more frequent in treated than in control animals. Liver lesions that exhibited positive dose trends include chronic inflammation and centrilobular fatty change in both sexes, mixed cell foci, and the combination of mixed cell foci and eosinophilic foci in females, and in males, basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344 rats.

Chronic Study of Triprolidine for Oncogenicity in Mice

Chronic Study of Triprolidine for Oncogenicity in Mice. Greenman, D. L., Sheldon, W., Schieferstein, G., Allen, R., and Allaben, W. T. (1995). Fundam. Appl. Toxicol. 25, 138-145. Triprolidine hydrochloride was fed to groups of 60 B6C3F1 mice per sex at dietary levels of 0, 500, 2000, or 4000 ppm (as the free base) for up to 2 years. Up to 12 mice of each sex and dose group were terminated after 65 weeks for hematology and clinical chemistry. The control and high-dose groups were examined histologically. A complete histopathological examination was performed on the remaining 48 mice from each dose group when removed from study due to moribund condition, early death, or terminal euthanization at 105 weeks. Triprolidine did not significantly alter the survival of either sex. High-dose male and mid- and high-dose female body weights were significantly less than controls at the end of the study. Significant trends toward lower frequency with increasing dose were noted in females for fatty change in the liver and lymphomas (combination of lymphocytic, mixed, and histiocytic lymphomas). Similar negative trends in males were for lymphocytic cellular infiltration in multiple organs and lung alveolar/bronchiolar adenomas or the combination of alveolar/bronchiolar adenomas or carcinomas. Significant trends toward increased frequency with increasing dose were found in female mice for lymphocytic infiltration in multiple organs and cytoplasmic alterations of the acinar cells of the parotid gland. Similar positive trends were found in males for cytoplasmic alterations of the parotid gland and various hepatocellular changes (e.g., hypertrophy and altered foci). While there was a positive dose-response trend for hepatocellular adenomas in males the combination of these and hepatocellular carcinomas eliminated the significant trend, and it was concluded that there was no evidence of a carcinogenic response to triprolidine in B6C3F1 mice. No effects considered to be adverse were observed in either sex at 500 ppm. Body weight depression was noted in females and liver toxicity was indicated in males at 2000 and 4000 ppm.

Chronic Study of Triprolidine for Oncogenicity in Mice

Triprolidine hydrochloride was fed to groups of 60 B6C3F1 mice per sex at dietary levels of 0, 500, 2000, or 4000 ppm (as the free base) for up to 2 years. Up to 12 mice of each sex and dose group were terminated after 65 weeks for hematology and clinical chemistry. The control and high-dose groups were examined histologically. A complete histopathological examination was performed on the remaining 48 mice from each dose group when removed from study due to moribund condition, early death, or terminal euthanization at 105 weeks. Triprolidine did not significantly alter the survival of either sex. High-dose male and mid- and high-dose female body weights were significantly less than controls at the end of the study. Significant trends toward lower frequency with increasing dose were noted in females for fatty change in the liver and lymphomas (combination of lymphocytic, mixed, and histiocytic lymphomas). Similar negative trends in males were for lymphocytic cellular infiltration in multiple organs and lung alveolar/bronchiolar adenomas or the combination of alveolar/bronchiolar adenomas or carcinomas. Significant trends toward increased frequency with increasing dose were found in female mice for lymphocytic infiltration in multiple organs and cytoplasmic alterations of the acinar cells of the parotid gland. Similar positive trends were found in males for cytoplasmic alterations of the parotid gland and various he-patocellular changes (e.g., hypertrophy and altered foci). While there was a positive dose-response trend for hepatocellular adenomas in males the combination of these and hepatocellular carcinomas eliminated the significant trend, and it was concluded that there was no evidence of a carcinogenic response to triprolidine in B6C3F1 mice. No effects considered to be adverse were observed in either sex at 500 ppm. Body weight depression was noted in females and liver toxicity was indicated in males at 2000 and 4000 ppm.

Triprolidine: 104-Week Feeding Study in Rats

The antihistamine, triprolidine hydrochloride, was fed at dietary concentrations of 0, 250, 1000, or 2000 ppm (as the free base) to groups of 60 Fischer 344 (F344) rats of each sex for up to 2 years to evaluate its potential carcinogenicity. Up to 12 per sex from each group were killed at 65 weeks, and hematology, clinical chemistry, and histopathology were evaluated. A complete histopatho-logical evaluation was performed on all other animals; survivors were killed at 2 years. Survival was significantly extended in tri-prolidine-treated males and females, particularly at the high dose. At the close of the study high-dose males and females had gained significantly less body weight than controls. Among rats killed at 65 weeks females in the mid- and high-dose groups weighed significantly less than controls, but weights of control and dosed males were not significantly different. The incidences of numerous lesions tended to decrease with increasing triprolidine dose. In females, clitoral gland adenomas, thyroid c-cell hyperplasia and neoplasia, mammary gland hyperplasia and fibroadenomas, and uterine stromal polyps, and in males, anterior pituitary gland adenomas, preputial gland neoplasia, thyroid c-cell hyperplasia, pancreatic islet neoplasia, mononuclear cell leukemia, and the combination of lymphocytic, histiocytic, and undifferentiated cell malignant lymphomas and mononuclear leukemia, all exhibited negative dose trends. Cytoplasmic alterations of the parotid gland and numerous liver lesions tended to be more frequent in treated than in control animals. Liver lesions that exhibited positive dose trends include chronic inflammation and centrilobular fatty change in both sexes, mixed cell foci, and the combination of mixed cell foci and eosinophilic foci in females, and in males, basophilic foci and eosinophilic foci. Triprolidine was not carcinogenic in F344 rats.

High-performance liquid chromatographic assay for the determination of paracetamol, pseudoephedrine hydrochloride and triprolidine hydrochloride

The different UV absorption characteristics of paracetamol, pseudoephedrine hydrochloride and triprolidine hydrochloride have been used to facilitate their determination in pharmaceutical preparations by HPLC. The method developed involves isocratic, reversed-phase chromatography. A ‘wavelength switching’ programme is preferred to the use of a compromise wavelength for all three compounds. This gives reasonable UV responses despite widely different UV characteristics and concentrations of drugs. The limits of quantitation are found to be within 200–700 μg ml −1 for paracetamol, 24–84 μg ml − for pseudoephedrine HCl and 1–4 μg ml − for triprolidine HCl. The method performs well in terms of precision and accuracy as indicated by linear regression analysis.

Mechanism of glycogenolytic action of histamine in rat hepatocytes.

The mechanism by which histamine induces glycogenolysis was investigated in rat hepatocytes. Histamine induced stimulation of glucose output in hepatocytes in a dose-dependent manner. The maximal effect of the glycogenolytic action of histamine, which was approximately 60% of the maximal glucagon action, was obtained at 10(-6) M. These effects were inhibited by H1 receptor antagonists triprolidine hydrochloride and tripelennamine but not by a H2 receptor antagonist cimetidine. Histamine also increased the activity of phosphorylase a. When 10(-6) M histamine and 5 x 10(-9) M glucagon were added simultaneously, the actions of these two agents were additive. In contrast, there was no additivity when 10(-6) M histamine and 10(-8) M angiotensin II were added. Histamine did not increase adenosine 3',5'-cyclic monophosphate at any doses tested but induced a rapid increase in the cytoplasmic free calcium concentration ([Ca2+]c). Histamine increased [Ca2+]c even in the presence of 1 microM extracellular calcium, an observation suggesting that histamine caused calcium release from an intracellular calcium pool(s). When [3H]inositol-labeled hepatocytes were incubated with histamine, radioactivity in the D-myo-inositol trisphosphate fraction was rapidly increased. These results indicate that histamine acts on rat hepatocytes mainly via H1 receptors and stimulates glycogenolysis by activating the calcium messenger system.

Sedation and histamine H1‐receptor antagonism: studies in man with the enantiomers of chlorpheniramine and dimethindene

1. The effects of 10 mg (+)- and (-)-chlorpheniramine and 5 mg (+)- and (-)-dimethindene on daytime sleep latencies, digit symbol substitution and subjective assessments of mood and well-being were studied in 6 healthy young adult humans. Each subject also took 5 mg triprolidine hydrochloride as an active control and two placebos. 2. Daytime sleep latencies were reduced with triprolidine, (+)-chlorpheniramine and (-)-dimethindene, and subjects also reported that they felt more sleepy after (+)-chlorpheniramine and (-)-dimethindene. Performance on digit symbol substitution was impaired with (+)-chlorpheniramine. 3. Changes in measures with (-)-chlorpheniramine and (+)-dimethindene were not different from changes with placebo. 4. In the present study, changes in measures of drowsiness and performance were limited to the enantiomers with high affinity for the histamine H1-receptor. These findings strongly suggest that sedation can arise from H1-receptor antagonism alone, and provide further support for the belief that the histaminergic system is concerned with the regulation of alertness in man.

Evaluation of the primary skin irritation and allergic contact sensitization potential of transdermal triprolidine

A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated thorough skin toxicity testing before and during initial clinical development. Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical pharmacokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued.

Evaluation of the Primary Skin Irritation and Allergic Contact Sensitization Potential of Transdermal Triprolidine

Evaluation of the Primary Skin Irritation and Allergic Contact Sensitization Potential of Trans-dermal Triprolidine. ROBINSON, M. K.., PARSELL, K. W., BRENEMAN, D. L., AND CRUZE, C. A. (1991). Fundam. Appl. Toxicol. 17, 103–119. A transdermal patch for the OTC antihistamine, triprolidine (TP), might provide benefits in terms of increased efficacy and reduced sedative side effects. However, concerns over potential irritant or allergic contact sensitization (ACS) skin reactions necessitated thorough skin toxicity testing before and during initial dinical development Initial effort was expended on development of a binary vehicle delivery system comprised of TP in 0.5% oleic acid (OA) in propylene glycol (PG). Rabbit skin irritation and Buehler guinea pig skin sensitization testing indicated that this TP/OA/PG formula had both skin irritation and ACS potential. Both tests underestimated, to some degree, the skin toxicities observed in later clinical testing. In clinical tests, skin irritation was due mainly to the OA–PG vehicle, but was enhanced in the presence of high TP concentrations. Of 26 subjects enrolled in a rising dose clinical phar-macokinetics study, one subject exposed twice to TP/OA/PG presented with delayed skin reactions suggestive of ACS. Positive diagnostic patch test results for this subject and four out of five other twice-exposed study subjects suggested that the TP/OA/PG formula had a very high ACS potential. Subsequent predictive clinical patch testing was conducted with a buffered aqueous TP formula which provided in vitro skin penetration of the drug equivalent to the TP/OA/PG formula. These clinical studies demonstrated that TP itself had no significant irritation potential but still induced ACS reactions in a high proportion of test subjects. The incidence of adverse skin reactions to TP was considered to be too high relative to the degree of improved therapeutic benefit of this delivery form. On this basis, all technology development effort was discontinued, © 1991 by the Society of Toxicology

Pharmacokinetics of Oral and Transdermal Triprolidine

In this open, nonrandomized, three-way crossover study, six healthy male volunteers received single doses of triprolidine (TPL) hydrochloride syrup orally (2.5 mg) and wore transdermal TPL patches (5 mg and 10 mg doses) to compare the pharmacokinetic profiles and dose tolerance of the two formulations. A washout period of at least 1 week was scheduled between the three dosing periods. Blood samples were collected at defined times, and plasma concentrations were determined using a radioimmunoassay. Maximum plasma drug concentration (Cmax) decreased from 5.6 +/- 2.9 ng/mL (mean +/- SD) with oral dosing to 2.0 +/- 1.0 ng/mL and 4.2 +/- 2.0 ng/mL following 5 mg and 10 mg transdermal doses, respectively. Time to reach peak concentration (tmax) increased from 2.0 +/- 1.2 hours with oral dosing to 12.0 +/- 5.9 and 14.3 +/- 9.9 hours following 5 mg and 10 mg transdermal doses, respectively. The differences between AUC0-alpha values with the oral syrup and the 5 mg and 10 mg transdermal doses were not significant when normalized to 2.09 mg (TPL base). The bioavailabilities of the 5 mg and 10 mg transdermal doses relative to the oral 2.09 mg doses were 0.89 +/- 0.32 and 1.04 +/- 0.33, respectively. Mild erythema and pruritus were the most common adverse effects secondary to TPL transdermal application. Drowsiness observed following oral TPL, was not evident following either transdermal dose. The results of this study, therefore, indicate that TPL can be absorbed transdermally, providing consistent plasma concentrations.

Extraction-spectrophotometric determination of some antihistaminic agents with fast green FCF

A rapid, simple, precise, accurate and highly sensitive method for the determination of some antihistaminic agents such as dimethindene maleate (DMM), embramine hydrochloride (EMH), isothipendyl hydrochloride (IPH), mebhydrolin napadisylate (MHn), methdilazine hydrochloride (MDH), promethazine hydrochloride (PMH), trimeprazine tartrate (TMT) and triprolidine hydrochloride (TPH) in bulk samples and pharmaceutical preparations is proposed. The method is based on the formation of a chloroform-soluble ion-association complex between the antihistaminic agent and Fast Green FCF at pH 5.0 with an absorption maximum at 620 nm. The composition of antihistaminic agent and Fast Green FCF in each ion-association complex is studied. The relative standard deviation of the proposed method is less than 1.3%, the percent recovery is 99.4–100.2% and the results are not significantly different from the standard methods at the 95% confidence level.

Microbial Transformation of the Antihistaminic Drug Triprolidine Hydrochloride

The production of a known mammalian metabolite of the antihistamine triprolidine through fungal metabolic transformation has been demonstrated. The filamentous fungus Cunninghamelta elegans ATCC 9245 was grown in Sabouraud dextrose broth containing triprolidine hydrochloride monohydrate. One major metabolite was extracted with methylene chloride, isolated by high-performance liquid chromatography, and identified by its proton-nuclear magnetic resonance and desorption chemical ionization mass spectral properties as hydroxy-methyl triprolidine (2-[1-(4-hydroxymethylphenyl)-3-(1-pyrrolidinyl-1-propenyl)] pyridine). After 240 h of incubation, the hydroxymethyl derivative represented ~55.0% of the initial dose. Fungal oxidation of hydroxymethyl triprolidine to the corresponding carboxylic acid triprolidine derivative (also a known mammalian triprolidine metabolite) was not observed. No mutagenic activity was observed for triprolidine and hydroxymethyl triprolidine by reversion of Salmonella typhimurium strains TA97, TA98, TA100, and TA104 at concentrations up to 1000 and 200 μg/plate, respectively. These results suggest that the fungal metabolism of triprolidine to the hydroxymethyl derivative occurs predominantly through pathways which do not result in mutagenic activation. Incubation of C. eleganswith triprolidine under an 18O2 atmosphere and subsequent electron impact mass spectral analysis of the hydroxymethyl triprolidine formed indicate that molecular oxygen was incorporated into the methyl group and suggest a mono-oxygenase catalyzed reaction. This study parallels previous studies on the mammalian metabolism of triprolidine and clearly indicates that the microbial transformation of triprolidine is a useful alternative for the synthesis of potential mammalian metabolites.

The simultaneous assay of triprolidine, pseudoephedrine and dextromethorphan in combined preparations by derivative-difference spectrophotometry

Difference spectrophotometric procedures are described for the assay of triprolidine hydrochloride, dextromethorphan hydrobromide and pseudoephedrine hydrochloride in Actifed preparations. Triprolidine is assayed by the measurement of the difference absorbance at 301 nm between equimolar solutions of the sample extract in 0.1 M sulphuric acid and 0.1 M sodium hydroxide in ethanol (20% v/v). Dextromethorphan and pseudoephedrine are assayed by measurement of the amplitudes in the second and fourth derivative spectra of the difference absorption spectrum of the sample solutions. The measured values are proportional to the concentrations of the drugs. The accuracy, precision and selectivity of the procedures are discussed. Applications of the assay are described for Actifed Compound Linctus, Actifed Syrup and Actifed Tablets.

An investigation of the H 1-receptor antagonist triprolidine: Pharmacokinetics and antihistaminic effects

A single oral dose of triprolidine hydrochloride, 0.04 mg/kg (mean dose 2.7 +/- SD 0.4 mg) was administered to seven healthy, fasting adult volunteers who had never been treated previously with H1-receptor antagonists. Blood sampling and intradermal tests with 0.01 ml of histamine phosphate (0.1 mg/ml) were performed at -0.25, 1, 2, 3, 4, 5, 6, 7, 8, and 12 hours after the dose. Wheal-and-flare circumferences were traced, and the areas were measured by planimetry. Pruritus was quantitated by use of a clinical score. Urine was collected in 6-hour pooled aliquots for a total of 24 hours. Serum and urine triprolidine concentrations were measured by high-performance liquid chromatography. Wheal-and-flare areas and pruritus decreased after the triprolidine dose. Suppression of mean flare size was statistically significant at 2, 3, 6 and 8 hours. Suppression of mean wheal size was not statistically significant at any time compared to predose values. The mean triprolidine serum half-life was 2.1 +/- 0.8 hours. The mean peak serum triprolidine concentration of 15.4 +/- 8.3 ng/ml occurred 2 hours after ingestion. No triprolidine was detected in the serum after 12 hours. The mean urinary excretion of unchanged triprolidine during 24 hours was 1.3 +/- 1.0% of the dose administered.

High pass digital filtering applied to quantitative UV spectrometry

High pass digital filtering is a novel method of data treatment for quantitative UV spectrometry in the presence of broad interfering bands. The test and standard spectra are digitally filtered using the binomial filter to remove low frequency components and a least squares fit of the standard to the test is then carried out. This paper reports a preliminary evaluation of the method, including a theoretical comparison with derivative spectrometry and the successful application to a typical problem in pharmaceutical analysis, the assay of the decongestant pseudoephedrine hydrochloride in the presence of the antihistamine triprolidine hydrochloride. The procedure should also be suitable for enhancing the specificity of other spectroscopic techniques.

The use of derivative and least-squares methods to analyse a polypharmaceutical product by UV spectrophotometry

Derivative UV spectrophotometry is well established for analysing pharmaceutical products containing more than one drug. By contrast, the least-squares method for over-determined systems is rarely used, because it is assumed that measurements at a large number of wavelengths are needed to obtain good results. Both methods have advantages, and their use in combination is useful for analysing polypharmaceuticals. A combination of derivative and least-squares methods was used to analyse tablets containing pseudoephedrine hydrochloride, triprolidine hydrochloride and dextromethorphan hydrobromide. Pseudoephedrine was determined by derivative spectrophotometry. The other drugs were determined by the least-squares method at higher wavelengths where pseudoephedrine does not absorb. Satisfactory precision for the least-squares method was obtained with a manual spectrometer measuring at six wavelengths and calculating the results with a microcomputer.

Pseudoephedrine and triprolidine in plasma and breast milk of nursing mothers.

Plasma and milk concentrations of pseudoephedrine and triprolidine were determined (by radioimmunoassay) in three lactating mothers over 12-48 h after ingestion of a combination medication containing 60 mg of pseudoephedrine hydrochloride and 2.5 mg of triprolidine hydrochloride monohydrate. Pseudoephedrine concentrations in milk were consistently higher than those in plasma. The total amount of drug in milk, as judged by areas under the respective curves (AUC), was two to three times greater than in plasma. Triprolidine concentrations in milk and plasma were more variable between subjects than those of pseudoephedrine. AUC values for milk and plasma were similar for one subject, while the plasma value exceeded that for milk in another woman. The fraction of the dose excreted in milk was estimated to be 0.4-0.7% for pseudoephedrine and 0.06-0.2% for triprolidine.

Trace analysis of the antihistamines methapyrilene hydrochloride, pyrilamine maleate and triprolidine hydrochloride monohydrate in animal feed, human urine and wastewater by high-performance liquid chromatography and gas chromatography with nitrogen—phosphorus detection

Toxicological evaluation of the antihistamines methapyrilene hydrochloride, pyrilamine maleate, and triprolidine hydrochloride monohydrate using methapyrilene hydrochloride as the positive indicator was investigated as part of a structure—activity relationship study in rats and mice. Prerequisites for the toxicological tests were the development of analytical procedures to certify the dose, homogeneity and stability of the drugs in animal feed and to monitor human urine for possible exposure and to ensure removal of the test agents from wastewater prior to its discharge into the environment. A high-performance liquid chromatographic (HPLC) system was developed using a fluorescence detector for the determination of methapyrilene hydrochloride and pyrilamine maleate in feed at levels as low as 100 ng/g and in human urine as low as 1 ng/g. An HPLC—UV procedure was developed for the determination of triprolidine hydrochloride monohydrate in feed at levels as low as 10 μ/g. Data concerning p-values, extraction efficiencies from feed and stability experiments in feed are presented for these antihistamines. A gas chromatographic procedure using a nitrogen—phosphorus detector was also developed for determining the three antihistamines in admixture in wastewater at levels as low as 10 ng/g.