Pharmaceuticals in equine medicine encompass a wide range of drugs and therapeutic agents used to treat various conditions in horses. These substances include analgesics, anti-inflammatories, antibiotics, sedatives, and anthelmintics, among others. Each class of pharmaceuticals is designed to address specific health issues, such as pain management, infection control, or parasitic infestations. The pharmacokinetics and pharmacodynamics of these drugs can vary significantly between horses and other species, necessitating careful consideration of dosage and administration methods. This page compiles peer-reviewed research studies and scholarly articles that explore the development, efficacy, safety, and regulatory aspects of pharmaceuticals used in equine healthcare.
Tyler CR, Filby AL, Bickley LK, Cumming RI, Gibson R, Labadie P, Katsu Y, Liney KE, Shears JA, Silva-Castro V, Urushitani H, Lange A, Winter MJ....Many factors have been considered in evaluations of the risk-benefit balance of hormone replacement therapy (HRT), used for treating menopausal symptoms in women, but not its potential risks for the environment We investigated the possible environmental health implications of conjugated equine estrogens (CEEs), the most common components of HRT, including their discharge into the environment, their uptake, potency, and ability to induce biological effects in wildlife. Influents and effluents from four U.K. sewage treatment works (STWs), and bile of effluent-exposed fish, were screened for six ...
Shank BR, Ofner CM.Pergolide mesylate (proprietary name Permax) is used to treat equine Cushing's syndrome. Since pergolide mesylate has been removed from the market, the tablets are no longer available. Therefore, pergolide mesylate preparations have to be compounded for veterinary use. Compounded oral liquid formulations have been given arbitrary beyond-use dates of 14 days (aqueous) to 90 days (oil based). The goal of this study was to determine the stability of a 0.2 mg/mL pergolide oral liquid prepared according to a previousy published formulation and stored at room temperature. The sample preparation and ...
Cordes B.The research article titled, “Effects of compounding and storage conditions on stability of pergolide mesylate” investigates the importance of adhering to the official US Pharmacopeia (USP) when formulating pergolide mesylate […]
Tevell Aberg A, Olsson C, Bondesson U, Hedeland M.This paper describes a study where the metabolism of the non-steroidal anti-inflammatory drug meloxicam was investigated in six horses and in the filamentous fungus Cunninghamella elegans. The metabolites identified were compared between the species, and then the fungus was used to produce larger amounts of the metabolites for future use as reference material. C. elegans proved to be a good model of phase I meloxicam metabolism in horses since all four metabolites found were the same in both species. Apart from the two main metabolites, 5'-hydroxymethylmeloxicam and 5'-carboxymeloxicam, a seco...
Barker SA.Beginning in 2004, the horseracing industry experienced an epidemic of drug positives for the amphetamine-like drug aminorex. Investigation of the therapeutic treatment of the horses called positive for this drug suggested that its source was from the administration of the anthelmintic levamisole. This study examines the urine concentrations of aminorex as a function of time following administration of synthetic, racemic aminorex. Confirmation of the presence of aminorex in urine samples from the horses known to be treated with levamisole is also presented as are data concerning the concentrat...
Vonaparti A, Lyris E, Panderi I, Koupparis M, Georgakopoulos C.In equine sport, theobromine is prohibited with a threshold level of 2 microg mL(-1) in urine, hence doping control laboratories have to establish quantitative and qualitative methods for its determination. Two simple liquid chromatography/mass spectrometry (LC/MS) methods for the identification and quantification of theobromine were developed and validated using the same sample preparation procedure but different mass spectrometric systems: ion trap mass spectrometry (ITMS) and time-of-flight mass spectrometry (TOFMS). Particle-free diluted urine samples were directly injected into the LC/MS ...
Ho EN, Leung DK, Leung GN, Wan TS, Wong AS, Wong CH, Soma LR, Rudy JA, Uboh C, Sams R.Administration studies of levamisole in horses were carried out using two different levamisole preparations, namely, levamisole hydrochloride oral bolus and levamisole phosphate injectable solution. These preparations were analysed in detail for the presence of aminorex-like impurities. Both levamisole preparations were found to contain 1-(2-mercaptoethyl)-4-phenyl-2-imidazolidinone (I) and 4-phenyl-2-imidazolidinone (II) as degradation impurities, but neither aminorex nor rexamino was detected in these preparations. After the administration of these preparations to horses, aminorex, rexamino,...
Davis JL, Kirk LM, Davidson GS, Papich MG.To determine the effects of temperature and light over a 35-day period on stability of pergolide mesylate after compounding in an aqueous vehicle. Methods: Evaluation study. Methods: Pergolide was compounded into a formulation with a final target concentration of 1 mg/mL. Aliquots of the formulation were then stored at -20 degrees, 8 degrees, 25 degrees, or 37 degrees C without exposure to light or at 25 degrees C with exposure to light for 35 days. Samples were assayed in triplicate by means of high-pressure liquid chromatography immediately after compounding and after 1, 7, 14, 21, and 35 da...
Barabas K, Milner R, Lurie D, Adin C.Cisplatin is a platinum chemotherapeutic used in a variety of malignancies. The antineoplastic activity occurs from DNA cross-links and adducts, in addition to the generation of superoxide radicals. Nephrotoxicity is the most well-known and potentially most clinically significant toxicity. Unfortunately, the mechanism for cisplatin nephrotoxicity has not been completely elucidated; however, many theories have been developed. Other toxicities include gastrointestinal, myelosuppression, ototoxicity and neurotoxicity. Saline diuresis is currently the most accepted way to prevent cisplatin nephrot...
You Y, Uboh CE, Soma LR, Guan F, Li X, Rudy JA, Chen J.A sensitive liquid chromatographic-tandem mass spectrometric method was developed and validated for screening, quantification, and confirmation of phenylbutazone and oxyphenbutazone in equine plasma. Analytes were recovered from plasma by liquid-liquid extraction followed by separation in a reversed-phase column and identification by mass spectrometry with selected reaction monitoring in negative electrospray ionization mode. Extraction recovery for both analytes was >80%. Limits of detection, quantification, and confirmation for both analytes were 0.01 microg/mL (S/N>or= 3), 0.05 microg...
De Leo M, Giorgi M, Saccomanni G, Manera C, Braca A.Tramadol is a centrally acting analgesic drug that has been used clinically for the last two decades to treat pain in humans. The clinical response of tramadol is strictly correlated to its metabolism, because of the different analgesic activity of its metabolites. O-Desmethyltramadol (M1), its major active metabolite, is 200 times more potent at the micro-receptor than the parent drug. In recent years tramadol has been widely introduced in veterinary medicine but its use has been questioned in some species. The aim of the present study was to develop a new sensible method to detect the whole ...
Kay AT, Bolt DM, Ishihara A, Rajala-Schultz PJ, Bertone AL.To assess analgesia, inflammation, potency, and duration of action associated with intra-articular injection of triamcinolone acetonide (TA), mepivacaine hydrochloride, or both in metacarpophalangeal (MCP) joints of horses with experimentally induced acute synovitis. Methods: 18 horses. Methods: Both forelimbs of each horse were injected with lipopolysaccharide (LPS) 3 times. After the first LPS injection, 1 forelimb of each horse was treated with intra-articular injection of mepivacaine (80 mg; n=6), TA (9 mg; 6), or mepivacaine with TA (same doses of each; 6) 12 hours after the initial LPS i...
Sleeper MM, McDonnell SM, Ely JJ, Reef VB.Enalapril is an angiotensin converting enzyme (ACE) inhibitor that is frequently used in human, feline and canine patients with cardiac disease. Its use has been associated with impotence in human patients. The purpose of this study was to evaluate if enalapril (0.5mg/kg PO, q24h) is likely to alter behavior in stallions and to assess its effect on ACE activity at the standard dose used in dogs and cats. Twelve pony stallions were evaluated by physical examination and echocardiography followed by treatment with enalapril (n=6) or placebo (n=6) for 2 months. After one month, blood was drawn and...
Gokbulut C, Cirak VY, Senlik B, Yildirim F, McKellar QA.This study aimed to determine the plasma disposition and faecal excretion of netobimin (NTB) and its respective metabolites as well as the efficacy against strongyles in horses following oral administration. Netobimin (10mg/kg) was administered orally to 8 horses. Blood and faecal samples were collected from 1 to 120h post-treatment and analysed by high performance liquid chromatography (HPLC). Using a chiral phase-based HPLC, plasma disposition of ABZSO enantiomers produced was also determined. Faecal strongyle egg counts (EPG) were performed by a modified McMaster's technique before and afte...
Barker SA.Advances in analytical technology now make it feasible to detect and confirm exceptionally low concentrations (pg to fg/mL) of drugs and their metabolites in equine biological fluids. These new capabilities complicate the regulatory interpretation of drug positives and bring into question the fair application of medication rules. Such approaches and policies are further complicated by the possibility that drug positives may arise from contamination of the equine environment on the backstretch of the race track. This manuscript provides data demonstrating that the general environment of the bac...
Letendre LT, Tessman RK, McClure SR, Kvaternick VJ, Fischer JB, Hanson PD.To determine pharmacokinetic parameters and variables, firocoxib concentrations in urine and plasma, urine-to-plasma ratios, and the urine depletion profile of firocoxib and to evaluate whether the pharmacokinetic behavior of firocoxib was governed by linear processes after multiple doses of firocoxib were administered IV and orally. Methods: 6 healthy female horses (5 Paint horses and 1 Quarter Horse) in experiment 1 and 12 healthy male and female horses in experiment 2. Methods: In experiment 1, 6 horses were orally administered firocoxib paste once daily for 12 consecutive days, and plasma ...
Tsitsimpikou C, Spyridaki MH, Georgoulakis I, Kouretas D, Konstantinidou M, Georgakopoulos CG.Flurbiprofen and its main acidic metabolites were detected in equine urine after a single-dose administration of 500 mg flurbiprofen to two 2.5-3.5-years-old mares, in order to be used in equine doping control routine analysis. The urine levels of the parent drug were determined using GC/MS. Five acidic metabolites were found in the urine. The structure of the proposed metabolites was confirmed by HRMS accurate mass measurements. The highest flurbiprofen concentration was 204 mug ml(-1) at 1-3 h post administration. Flurbiprofen could be detected for 24-37 h in urine using the standard screeni...
Yamada M, Aramaki S, Kurosawa M, Kijima-Suda I, Saito K, Nakazawa H.The use of anabolic steroids in racehorses is strictly regulated. We have developed a method for the simultaneous analysis of 11 anabolic steroids: fluoxymesterone, 17alpha-methyltestosterone, mestanolone, methandienone, methandriol, oxymetholone, boldenone, furazabol, methenolone, nandrolone, and stanozolol, for possible application to a doping test in racehorses. We selected 15 kinds of target substances for a doping test from the main metabolites of these anabolic steroids, and established a method for simultaneous analysis. Urine was hydrolyzed and subjected to solid-phase extraction. Then...
Davidson GS.Anesthetization of large animals, such as the horse, is a challenge for veterinarians and compounding pharmacists. This article discusses the technique of intravenous anesthesia by using a combination of xylazine and ketamine in the horse for short-term unconsciousness; a combination of xylazine, diazepam, and ketamine, for improved sedation and muscle relaxation; and a combination of xylazine, ketamine, and guaifenesin, referred to as Triple Drip, for the maximum 1-hour duration of unconsciousness. Compounding pharmacists that have the facilities and training required to prepare sterile compo...
Fidani M, Gamberini MC, Pasello E, Palazzoli F, Dimasi T, Montana M.A development of a rapid and sensitive LC-MS/MS method for the simultaneous detection of active ingredients of the euthanasic veterinarian drug Tanax mixture is described. The method proposed, with a retention time of few minutes (6 min) was developed for an equine serum sample with solid-phase extraction (S.P.E). This S.P.E. procedure has been revealed useful for the determination of very low concentrations of Tanax analytes (0.05-1 ng/ml). The method was validated in terms of specificity/selectivity, sensitivity, recovery and precision.
Maxwell LK, Bentz BG, Bourne DW, Erkert RS.Recent outbreaks of equine herpes virus type-1 infections have stimulated renewed interest in the use of effective antiherpetic drugs in horses. The purpose of this study was to investigate the pharmacokinetics of valacyclovir (VCV), the prodrug of acyclovir (ACV), in horses. Six adult horses were used in a randomized cross-over design. Treatments consisted of 10 mg/kg ACV infused intravenously, 5 g (7.7-11.7 mg/kg) VCV delivered intragastrically (IG) and 15 g (22.7-34.1 mg/kg) VCV administered IG. Serum samples were obtained at predetermined times for acyclovir assay using high-performance li...
Yamada M, Aramaki S, Hosoe T, Kurosawa M, Kijima-Suda I, Saito K, Nakazawa H.Fluoxymesterone, an anabolic steroid with the 17alpha-methyl,17beta-hydroxy group, has been developed as an oral formulation for therapeutic purposes. However, it is also used illegally in racehorses to enhance racing performance. In this study, we detected 9alpha-fluoro-17,17-dimethyl-18-norandrostane-4,13-dien-11beta-ol-3-one by gas chromatography/mass spectrometry (GC/MS), which has not been reported as a fluoxymesterone metabolite so far in horse. It was synthesized for use as a reference standard, and characterized on the basis of (1)H NMR and (13)C NMR spectra, as well as GC/MS EI mass s...
Longhofer SL, Reinemeyer CR, Radecki SV.The efficacy of top-dress antiinflammatory drugs ultimately depends on a patient's willingness to consume treated feed. The current study compares the palatability of two phenylbutazone top-dress formulations (Equipalazone Powder, Dechra Pharmaceuticals, and Pro-Dynam, VetXX, Ltd.) and a suxibuzone top-dress formulation (Danilon Equidos, Janssen Animal Health). Results of a three-period, crossover study on 18 healthy horses showed that Pro-Dynam was significantly less palatable, with significantly less consumption of treated feed compared with either Equipalazone Powder or Danilon Equidos. The...
Bolt DM, Ishihara A, Weisbrode SE, Bertone AL.To evaluate the effects of triamcinolone acetonide (TA), sodium hyaluronate (HA), amikacin sulfate (AS), and mepivacaine hydrochloride (MC) on articular cartilage morphology and matrix composition in lipopolysaccharide (LPS)-challenged and unchallenged equine articular cartilage explants. Methods: 96 articular cartilage explants from 4 femoropatellar joints of 2 adult horses. Methods: Articular cartilage explants were challenged with LPS (100 ng/mL) or unchallenged for 48 hours, then treated with TA, HA, AS, and MC alone or in combination for 96 hours or left untreated. Cartilage extracts were...
Yamada M, Aramaki S, Kurosawa M, Saito K, Nakazawa H.Methandienone, methandriol, and oxymetholone, which are anabolic steroids possessing 17alpha-methyl and 17beta-hydroxy groups, were developed as oral formulations for therapeutic purposes. However, they have been used in racehorses to enhance racing performance. In humans, it has been reported that structurally related anabolic steroids having the 17alpha-methyl and 17beta-hydroxy groups, including 17alpha-methyltestosterone, mestanolone, methandienone, methandriol, and oxymetholone, have metabolites in common. In this study, we found that metabolites common to those of 17alpha-methyltestoster...
Colas C, Popot MA, Garcia P, Bonnaire Y, Bouchonnet S.LC/ESI-MS n methods have been previously set up to detect the administration of (i) Harpagophytum and (ii) preparations containing a plant capable of anti-stress properties: Eleutherococcus senticosus. Harpagoside has been found to be the main indicator of Harpagophytum administration in the horse. These methods have been applied to a large number of horse urine samples of various origins. Regarding the detection of Harpagophytum administration, harpagoside, harpagide and 8-para-coumaroyl harpagide were detected together in only one sample out of 317. Eleutheroside E was found to be the main i...
Giri SN, Margolin SB.The effectiveness of pirfenidone ointment against thermoplasty-induced acute foreleg lameness in a double-blind study, and against acute and chronic lameness of musculoskeletal origin in an open multi-centered field trial was evaluated in this study. Thermoplasty was performed on both inner forelegs at designated locations of each horse under anesthetics. A 10% pirfenidone or placebo ointment was topically applied starting 24 hours after the thermoplasty three times daily for 7 days. For acute and chronic lameness of musculoskeletal origin, pirfenidone ointment was also applied one to three ti...
Davidson GS.Anesthetization of large animals, such as the horse, is a challenge for veterinarians and compounding pharmacists. This article discusses the technique of intravenous anesthesia by using a combination of xylazine and ketamine in the horse for short-term unconsciousness; a combination of xylazine, diazepam, and ketamine, for improved sedation and muscle relaxation; and a combination of xylazine, ketamine, and guaifenesin, referred to as Triple Drip, for the maximum 1-hour duration of unconsciousness. Compounding pharmacists that have the facilities and training required to prepare sterile compo...
Wynne PM, Vine JH, Amiet RG.Protopine was extracted from Fumaria officinalis and purified by column chromatography. Urine samples were collected from horses and a human volunteer that had been administered either F. officinalis or protopine free base. Plant and urine samples were acetylated and analysed by GCMS after solid-phase extraction (SPE). The urinary metabolites of protopine were identified as 4,6,7,13-tetrahydro-9,10-dihydroxy-5-methyl-benzo[e]-l,3-benzodioxolo [4,5-1][2] benzazecin-12(5H)-one, 4,6,7,13-tetrahydro-10-hydroxy-9-methoxy-5-methyl-benzo[e]-1,3-benzodioxolo[4,5-1][2] benzazecin-12(5H)-one and 4,6,7,1...
Colahan PT, Bailey JE, Johnson M, Rice BL, Chou CC, Cheeks JP, Jones GL, Yang M.Following the regimen used to treat equine protozoal myeloencephalitis, sulfadiazine (20 mg/kg) and pyrimethamine (1mg/kg) were administered orally once daily to 12 physically conditioned Thoroughbred horses for 4 consecutive days. The horses were randomly assigned to two test groups in a crossover design, with each horse serving as its own control. A stepwise exercise stress test was conducted to exhaustion. No effect on athletic performance was observed, and only marginal effects were noted in some hematologic and serochemical measurements, including decreased total white blood cell counts, ...
Olsén L, Bondesson U, Broström H, Tjälve H, Ingvast-Larsson C.The pharmacokinetics of the histamine H(1)-antagonist cetirizine and its effect on histamine-induced cutaneous wheal formation were studied in six healthy horses following repeated oral administration. After three consecutive administrations of cetirizine (0.2 mg/kg body weight, bw) every 12h, the trough plasma concentration of cetirizine was 16+/-4 ng/mL (mean+/-SD) and the wheal formation was inhibited by 45+/-23%. After four additional administrations of cetirizine (0.4 mg/kg bw) every 12 h, the trough plasma concentration was 48+/-15 ng/mL and the wheal formation was inhibited by 68+/-11%....
Göktaş EF, Kabil E, Arıöz F.Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in therapeutic doses in human and veterinary medicine for the treatment of inflammation, pain, and fever. A method for the simultaneous determination of nine NSAIDs, known as therapeutic prohibited substances, in equine urine was developed and fully validated according to the European Commission Decision 2002/657/EC and Association of Official Racing Chemists criteria. The validation was performed for naproxen, flunixin, ketoprofen, diclofenac, eltenac, meclofenamic acid, phenylbutazone, vedaprofen, and carprofen in equine urine i...
Wynne PM, Vine JH, Amiet RG.The influence of sampling variables on the concentration of the dopamine metabolites 3-methoxytyramine (3MT), dihydroxyphenylacetic acid (DOPAC) and homovanilic acid (HVA) was examined in equine urine. A logarithmic transformation of the data for all horses gave distribution which approximated the normal distributions for each metabolite. The mean urinary concentration of 3 MT in horses was 214 ng/mL and the application of a threshold with a probability of 1 in 10,000 gave an actionable level of 4 microg/mL. Environmental variables were not forensically significant in determining the populatio...
Sams R, Pizzo P.The possibility exists that ketamine, or ketamine in combination with xylazine, is being used illicitly to affect the performance of racehorses. This study was undertaken to identify the metabolites of ketamine in the urine of adult horses and to evaluate methods for detecting and confirming ketamine administration. Detection of ketamine and two ketamine metabolites is described using thin-layer chromatography (TLC) and their identities are confirmed by comparing their mass spectra and gas chromatographic retention times with those of authentic standards.
Clarke CR, Burrows GE, MacAllister CG, Spillers DK, Ewing P, Lauer AK.Single-dose pharmacokinetic variables of pyrimethamine were studied in horses. Pyrimethamine (1 mg/kg of body weight) was administered IV and orally to 6 adult horses, and plasma samples were obtained at frequent intervals thereafter. Plasma pyrimethamine concentration was assayed by gas chromatography, and concentration-time data were analyzed, using a pharmacokinetic computer program. The IV and oral administration data were best described by 3-compartment and 1-compartment models, respectively. The median volume of distribution at steady state after IV administration was 1,521 ml/kg and the...
Jaussaud P, Guieu D, Courtot D, Barbier B, Bonnaire Y.A tolfenamic acid metabolite, a hydroxylated product, has been identified in equine plasma and urine samples using gas chromatography-mass spectrometry in the electron-impact and chemical-ionization modes. The method also allows the qualitative monitoring of the elimination of the drug and its metabolites from plasma. The two compounds are detected up to 48 and 24 h, respectively, after a single oral administration of a 30 mg/kg dose. The simultaneous detection of the two products increases the reliability of anti-doping control analysis.
Pearson W.Standardbred trainers from 1 racetrack and 7 off-track training facilities were surveyed to determine the most common drugs, and prevalence of concurrent herb administration. Furosemide (on-track) and anti-inflammatory drugs (off-track) were the most common drugs administered. Among horses on-track, 9.8% received herbs compared with 13.8% off-track horses; 67% and 58% of these horses, respectively, received concurrent drugs. Les soigneurs de Standardbreds de 1 piste de course et de 7 installations d’entraînement hors piste ont été interrogés afin de déterminer les médicaments les plus...
Wong ASY, Leung GNW, Leung DKK, Wan TSM.Anabolic steroids are banned substances in equine sports. Gas chromatography-mass spectrometry (GC-MS) has been the traditional technique for doping control analysis of anabolic steroids in biological samples. Although liquid chromatography-mass spectrometry (LC/MS) has become an important technique in doping control, the detection of saturated hydroxysteroids by LC-MS remains a problem due to their low ionization efficiency under electrospray. The recent development in fast-scanning gas-chromatography-triple-quadrupole mass spectrometry (GC-MS/MS) has provided a better alternative with a sign...
Whittem T.This article presents in easily accessible form a collection of drug names and dose rates for the drugs recommended or referred to by the authors of the individual articles in this issue. Although the formulary provides recommendations for drug use, the reader is cautioned that the responsibility for the choice of agent, formulation, dose, and dose interval lies with the clinician. The author also addresses regulations that govern the use of drugs in competition horses.
Pemberton AD, Slater JS, Milne EM.A method for flunixin detection in equine serum extracts involving thin layer chromatography, spraying the chromatogram with alkaline sodium hypochlorite solution and heating with a detection limit of 50 ng ml-1 is described.
Göktaş EF, Kabil E, Yatanaslan L, Güneş E, Dirikolu L.Caffeine is a naturally occurring alkaloid and it is metabolized to paraxanthine, theophylline and theobromine. Analysis of caffeine and its metabolites is challenging since the metabolites theophylline and paraxanthine generate similar product and precursor ions. In this study, a new method was developed for the simultaneous analysis of caffeine, paraxanthine, theobromine and theophylline in horse urine using gas chromatography-mass spectrometry (GC-MS). Urine samples were treated using solid-phase extraction followed by the elution with dichloromethane-isopropanol (90:10) after the pH was ad...
Karatt TK, Sathiq MA, Laya S, Kal AKK, Subhahar MB, Muhammed Ajeebsanu MP, Philip M, Caveney MR, Graiban FM.Nonsteroidal selective androgen receptor modulators (SARMs) are a novel class of compounds that have not yet been clinically approved; however, they appear to have a better anabolic/androgenic ratio than steroids and cause slighter side effects. Sports drug testing laboratories are required to maintain continuously updated doping control analytical methods in light of the widespread misuse of SARMs in elite and amateur sports. This paper describes the metabolic conversion of SARM GSK2881078 in thoroughbred horses following oral administration and in vitro with equine liver microsomes. A liquid...
Davis LE.Adverse drug reactions occasionally occur in the horse. The majority can be anticipated and avoided. The practicing veterinarian should understand the various types of adverse reactions as well as their mechanisms so that should such a reaction occur, the practitioner can promptly recognize the problem and institute corrective measures.
Momose A, Tsuji T.When sulpyrine and aminopyrine are administered to the horse, unchanged aminopyrine and its metabolites, 4-methylaminoantipyrine and 4-aminoantipyrine, are detected in the urine by means of thin-layer chromatography (TLC) and gas liquid chromatography. Further identification of aminopyrine and these metabolites was carried out by the gas chromatography-mass spectrometry (GC-MS) method. The procedures for separation and identification are as follows : The excretions were adjusted to pH 9 with ammonium hydroxide and extracted with chloroform. The extract was separated by TLC. The spots were loca...