The confirmation and control of metabolic caffeine in standardbred horses after administration of theophylline

Todi, F.; Mendonça, Monique Culturato Padilha; Ryan, Michael E.; Herskovits, Peter

doi:10.1046/j.1365-2885.1999.00226.x

Cited by 11 publications

(16 citation statements)

References 4 publications

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“…The methylation of theophylline in man and horses has earlier been described by Tang‐Liu and Riegelmann and Todi et al ., respectively. No detectable levels of caffeine were monitored in plasma after oral administration.…”

Section: Resultsmentioning

confidence: 99%

“…Actually, Todi et al . suggested to establish a urinary threshold for caffeine of 1000 ng/mL and a plasma threshold of 250 ng/mL to account for metabolic caffeine after administration of theophylline to racehorses.…”

Section: Discussionmentioning

confidence: 99%

“…[22] In contrast to other dimethylated xanthines, theophylline has been reported to undergo methylation resulting in the formation of caffeine. [23] According to Löscher [6] the half-life of theophylline varies in different animal species and has been estimated in horses to be 10-17 h.…”

Section: Theophyllinementioning

confidence: 99%

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Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations

Machnik

Kaiser²,

Koppe³

et al. 2016

Drug Testing and Analysis

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Methylxanthines positives in competition samples have challenged doping control laboratories and racing jurisdictions since methylxanthines are naturally occurring prohibited substances and often constituents of feed. For theobromine, an international threshold (renamed in International Residue Limit, IRL) of 2 µg/mL in urine has been established. On the basis of the data presented herein, a threshold or rather an IRL for theobromine in plasma of 0.3 µg/mL was proposed and was thereupon approved by the International Federation of Horseracing Authorities (IFHA). Official recommendations for reporting caffeine and theophylline are still lacking. The aim of the study was to investigate IRLs for theobromine in blood and for caffeine and theophylline in blood and urine. Therefore, a set of six administrations were carried out including both single i.v. and single oral administrations of caffeine, theobromine and theophylline. Plasma and urine concentrations were determined using a validated liquid chromatography-tandem mass spectrometry (LC-MS/MS). Applying the Toutain model approach an effective plasma concentration (EPC) of caffeine was estimated at 3.05 µg/mL, irrelevant concentrations in blood (IPC) and urine (IUC) approached 6 and 12 ng/mL, respectively. EPC of theobromine was calculated with 3.80 µg/mL, and irrelevant concentrations of theobromine were determined at 8 ng/mL in plasma and at 142 ng/mL in urine. Toutain modelling of the theophylline data produced an EPC, IPC, and IUC of 3.20 µg/mL, 6 ng/mL, and 75 ng/mL, respectively. The obtained irrelevant concentrations were used to postulate IRLs for theobromine in plasma and for caffeine and theophylline in plasma and urine. Copyright © 2016 John Wiley & Sons, Ltd.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations

Machnik

Kaiser²,

Koppe³

et al. 2016

Drug Testing and Analysis

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“…Approximately 150 spectra of different libraries of compounds were studied. The following groups of molecules were investigated: sulfonamides,20–36 benzimidazoles,37–48 carnitines,49–54 amphetamines,55–60 amino acids,61–80 and purines 81–83. It was observed that each of the above groups produced specific fragment ions and neutral mass losses, depending on the functional groups present in the molecules.…”

Section: Resultsmentioning

confidence: 99%

Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non‐peptidic combinatorial compounds

Klagkou

Pullen

Harrison

et al. 2003

Rapid Comm Mass Spectrometry

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Combinatorial chemistry is widely used within the pharmaceutical industry as a means of rapid identification of potential drugs. With the growth of combinatorial libraries, mass spectrometry (MS) became the key analytical technique because of its speed of analysis, sensitivity, accuracy and ability to be coupled with other analytical techniques. In the majority of cases, electrospray mass spectrometry (ES-MS) has become the default ionisation technique. However, due to the absence of fragment ions in the resulting spectra, tandem mass spectrometry (MS/MS) is required to provide structural information for the identification of an unknown analyte. This work discusses the first steps of an investigation into the fragmentation pathways taking place in electrospray tandem mass spectrometry. The ultimate goal for this project is to set general fragmentation rules for non-peptidic, pharmaceutical, combinatorial compounds. As an aid, an artificial intelligence (AI) software package is used to facilitate interpretation of the spectra. This initial study has focused on determining the fragmentation rules for some classes of compound types that fit the remit as outlined above. Based on studies carried out on several combinatorial libraries of these compounds, it was established that different classes of drug molecules follow unique fragmentation pathways. In addition to these general observations, the specific ionisation processes and the fragmentation pathways involved in the electrospray mass spectra of these systems were explored. The ultimate goal will be to incorporate our findings into the computer program and allow identification of an unknown, non-peptidic compound following insertion of its ES-MS/MS spectrum into the AI package. The work herein demonstrates the potential benefit of such an approach in addressing the issue of high-throughput, automated MS/MS data interpretation.

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“…LC/MS methods of analysis for salicylic acid, 6) acetaminophen, [6][7][8] theophylline, 9,10) barbiturates, 11) and bromvalerylurea [12][13][14] have been reported, but our examination of the literature has not revealed any method of simultaneous analysis for all of these from biological samples.…”

mentioning

confidence: 83%

Method for Screening and Quantitative Determination of Serum Levels of Salicylic Acid, Acetaminophen, Theophylline, Phenobarbital, Bromvalerylurea, Pentobarbital, and Amobarbital Using Liquid Chromatography/Electrospray Mass Spectrometry

Hori

Fujisawa

Shimada

et al. 2006

Biological & Pharmaceutical Bulletin

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The confirmation and control of metabolic caffeine in standardbred horses after administration of theophylline

Cited by 11 publications

References 4 publications

Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations

Control of methylxanthines in the competition horse: pharmacokinetic/pharmacodynamic studies on caffeine, theobromine and theophylline for the assessment of irrelevant concentrations

Approaches towards the automated interpretation and prediction of electrospray tandem mass spectra of non‐peptidic combinatorial compounds

Method for Screening and Quantitative Determination of Serum Levels of Salicylic Acid, Acetaminophen, Theophylline, Phenobarbital, Bromvalerylurea, Pentobarbital, and Amobarbital Using Liquid Chromatography/Electrospray Mass Spectrometry

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