Pharmacokinetics of Methylphenidate in the Rat Using Single-Ion Monitoring GLC-Mass Spectrometry

Gál, J.; Hodshon, Barbara J.; Pintauro, C.; Flamm, Bernd; Cho, A.K.

doi:10.1002/jps.2600660633

Cited by 34 publications

(7 citation statements)

References 19 publications

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“…This method has a sensitivity of < 1 ng/ml. (Segal et al, 1976;Perel & Dayton, 1977) which noted that although the half life of the deesterification to ritalinic acid, at 37°C, by plasma or serum was similar; 11.5 h (range 9.0-14.3 h) the addition of EDTA prevents the occurrence of this hydrolytic process for at least 24 h. It is of interest that a previous communication reported that methylphenidate was bound to human albumin (crystaline 4% W/V) to the extent of 12% (Faraj et al, 1974 (Gal, Hodshon, Pintauro, Flamm & Cho, 1977), the use of a onecompartment equation has been shown to introduce negligible (1% to 5%) errors in the calculation of drug clearances for many drugs, including lipophilic psychoactive agents (Dvorchik & Vesell, 1978). The pharmacokinetic parameters calculated for each patient are listed in Table 1.…”

Section: Subjects and Specinensmentioning

confidence: 94%

Pharmacokinetics of methylphenidate in hyperkinetic children.

Hungund¹,

Jm²,

Mj³

et al. 1979

Brit J Clinical Pharma

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1 Pharmacokinetic study has been carried out following oral administration of 10‐20 mg of methylphenidate hydrochloride to four behaviorally disorders children. 2 It is indicated that the drug is metabolized to ritalinic acid with an apparent plasma half life of 2.5 h. 3 The variability in magnitude of plasma concentration seems to be due not to its metabolism to ritalinic acid but due to the variability in the apparent volume of distribution. 4 The brief half life of methylphenidate which parallels the short duration of action of methylphenidate in behaviorally disordered children may be explained in part by its low protein binding which results in high percentage of free drug being made available for metabolism to pharmacologically inactive metabolites.

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Section: Subjects and Specinensmentioning

confidence: 94%

Pharmacokinetics of methylphenidate in hyperkinetic children.

Hungund¹,

Jm²,

Mj³

et al. 1979

Brit J Clinical Pharma

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“…Brain levels of these substances reach higher concentrations than those found in plasma. Indeed, brain concentrations can be around 8 times the plasma concentration (methylphenidate, Gal et al, 1977;d-amphetamine, Riffee et al, 1978). Given these considerations, we chose concentrations of 100 ng/ml (0.37 M; low), 200 ng/ml (0.74 M; medium) and 300 ng/ml (1.11 M; high) for methylphenidate and 300 ng/ml (1.63 M; low), 600 ng/ml (3.26 M; medium) and 900 ng/ml (4.89 M; high) for d-amphetamine.…”

Section: Accepted Manuscriptmentioning

confidence: 99%

Drug therapies for attentional disorders alter the signal-to-noise ratio in the superior colliculus

2009

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Despite high levels of use, the mechanism of action of effective pharmacotherapies in attention deficit hyperactivity disorder (ADHD) is unknown. It has recently been hypothesized that one site of therapeutic action is the midbrain superior colliculus, a structure traditionally associated with visual processing, but also strongly implicated in distractibility, a core symptom of ADHD. We used male juvenile Wistar rats to examine the effects of therapeutically relevant doses of methylphenidate and d-amphetamine on collicular activity in vitro. Here we report a novel shared mechanism of the two drugs whereby they enhance the signal-to-noise ratio in the superior colliculus. The effects on the signal-to-noise ratio were mediated by serotonin (5-HT) via a pre-synaptic mechanism. This modulatory action would bias the system towards salient events and lead to an overall decrease in distractibility.

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“…With similar levels in the brain as found in blood plasma for the majority of animals, the results are partially in line with previous data using a different route of drug administration. Gal et al administered MPH via intravenous injection . While they found a linear correlation between plasma and brain levels, they also found much higher levels of MPH in the brain than the blood plasma.…”

Section: Resultsmentioning

confidence: 99%

“…Gal et al administered MPH via intravenous injection. [56] While they found a linear correlation between plasma and brain levels, they also found much higher levels of MPH in the brain than the blood plasma. One possible reason is the difference in doses.…”

Section: Experimental Application: Correlation Of Brain To Plasma Mphmentioning

confidence: 95%

Fast quantitative determination of methylphenidate levels in rat plasma and brain ex vivo by MALDI‐MS/MS

et al. 2015

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This study presents a simple and sensitive high-throughput matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometry (MALDI-MS/MS) method for ex vivo quantification of methylphenidate (MPH) in rat plasma and brain. The common MALDI matrix alpha-cyano-4-hydroxycinnamic acid was used to obtain an optimal dried droplet preparation. For method validation, standards diluted in plasma and brain homogenate prepared from untreated (control) rats were used. MPH was quantified within a concentration range of 0.1-40 ng/ml in plasma and 0.4-40 ng/ml in brain homogenate with an excellent linearity (R ≥ 0.9997) and good precision. The intra-day and inter-day accuracies fulfilled the FDA's ±15/20 critera. The recovery of MPH ranged from 93.8 to 98.5% and 87.2 to 99.8% in plasma and homogenate, respectively. We show that MPH is successfully quantified in plasma and brain homogenate of rats pre-treated with this drug using the internal standard calibration method. By means of this method, a linear correlation between plasma and brain concentration of MPH in rodents pre-treated with MPH was detected. The simple sample preparation based on liquid-liquid extraction and MALDI-MS/MS measurement requires approximately 10 s per sample, and this significantly reduces analysis time compared with other analytical methods. To the best of our knowledge, this is the first MALDI-MS/MS method for quantification of MPH in rat plasma and brain. Copyright © 2015 John Wiley & Sons, Ltd.

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Pharmacokinetics of Methylphenidate in the Rat Using Single-Ion Monitoring GLC-Mass Spectrometry

Cited by 34 publications

References 19 publications

Pharmacokinetics of methylphenidate in hyperkinetic children.

Pharmacokinetics of methylphenidate in hyperkinetic children.

Drug therapies for attentional disorders alter the signal-to-noise ratio in the superior colliculus

Fast quantitative determination of methylphenidate levels in rat plasma and brain ex vivo by MALDI‐MS/MS

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