Ritalinic acid in urine: Impact of age and dose

Hydrolysis of the methyl ester (±)-threo-methyl phenidate afforded the free acid in 40% yield,viz.(±)-threo-ritalinic acid, C13H17NO2. Hydrolysis and subsequent crystallization were accomplished at pH values between 5 and 7 to yield colourless prisms which were analysed by X-ray crystallography. Crystals of (±)-threo-ritalinic acid belong to theP21/nspace group and form intermolecular hydrogen bonds. An antiperiplanar disposition of the H atoms of the (HOOC—)CH—CHpygroup (py is pyridine) was found in both the solid (diffraction analysis) and solution state (NMR analysis). It was also determined that (±)-threo-ritalinic acid conforms to the minimization of negativegauche+–gauche−interactions.

Download Full-text

Potential trends in Attention Deficit Hyperactivity Disorder (ADHD) drug use on a college campus: Wastewater analysis of amphetamine and ritalinic acid

The Science of The Total Environment ◽

10.1016/j.scitotenv.2013.02.020 ◽

2013 ◽

Vol 450-451 ◽

pp. 242-249 ◽

Cited By ~ 49

Author(s):

Daniel A. Burgard ◽

Rick Fuller ◽

Brian Becker ◽

Rebecca Ferrell ◽

M.J. Dinglasan-Panlilio

Keyword(s):

Attention Deficit Hyperactivity Disorder ◽

Drug Use ◽

Attention Deficit ◽

College Campus ◽

Wastewater Analysis ◽

Hyperactivity Disorder ◽

Ritalinic Acid

Download Full-text

Stability of Methylphenidate under Various pH Conditions in the Presence or Absence of Gut Microbiota

Pharmaceuticals ◽

10.3390/ph14080733 ◽

2021 ◽

Vol 14 (8) ◽

pp. 733

Author(s):

Julia Aresti-Sanz ◽

Markus Schwalbe ◽

Rob Rodrigues Pereira ◽

Hjalmar Permentier ◽

Sahar El Aidy

Keyword(s):

Gut Microbiota ◽

In Silico Analysis ◽

Intestinal Bacteria ◽

Inactive Form ◽

High Interindividual Variability ◽

Ritalinic Acid ◽

Ph Conditions ◽

Small Intestinal ◽

The Stability ◽

Hydrolysis Of

Methylphenidate is one of the most widely used oral treatments for attention-deficit/hyperactivity disorder (ADHD). The drug is mainly absorbed in the small intestine and has low bioavailability. Accordingly, a high interindividual variability in terms of response to the treatment is known among ADHD patients treated with methylphenidate. Nonetheless, very little is known about the factors that influence the drug’s absorption and bioavailability. Gut microbiota has been shown to reduce the bioavailability of a wide variety of orally administered drugs. Here, we tested the ability of small intestinal bacteria to metabolize methylphenidate. In silico analysis identified several small intestinal bacteria to harbor homologues of the human carboxylesterase 1 enzyme responsible for the hydrolysis of methylphenidate in the liver into the inactive form, ritalinic acid. Despite our initial results hinting towards possible bacterial hydrolysis of the drug, up to 60% of methylphenidate is spontaneously hydrolyzed in the absence of bacteria and this hydrolysis is pH-dependent. Overall, our results indicate that the stability of methylphenidate is compromised under certain pH conditions in the presence or absence of gut microbiota.

Download Full-text

Gas-Liquid Chromatographic Procedure for Measurement of Methylphenidate Hydrochloride and Its Metabolite, Ritalinic Acid, in Urine

Clinical Chemistry ◽

10.1093/clinchem/20.4.440 ◽

1974 ◽

Vol 20 (4) ◽

pp. 440-443 ◽

Cited By ~ 18

Author(s):

Rhondda Wells ◽

Keith B Hammond ◽

Denis O Rodgerson

Keyword(s):

Aqueous Phase ◽

Small Proportion ◽

Internal Standard ◽

Chromatographic Column ◽

Unchanged Drug ◽

Ritalinic Acid ◽

Chromatographic Procedure ◽

Normal Urine ◽

Liquid Chromatographic ◽

Drug Free

Abstract A gas-liquid chromatographic procedure has been developed for measuring methylphenidate and its metabolite, ritalinic acid, in urine. The unchanged drug is extracted into chloroform from alkalinized urine together with an internal standard, diphenhydramine. The solvent is removed, the residue dissolved in ethanol, and aliquots are injected into a gas-chromatographic column containing 3% OV-17. Ritalinic acid is recovered from the urine by lyophilizing the aqueous phase remaining after the unchanged methylphenidate is extracted into chloroform. The ritalinic acid is methylated with diazomethane to form methylphenidate, which is then assayed as described. Recovery of methylphenidate added to normal urine was quantitative and reproducible (CV, 3.2%). Ritalinic acid added to drug-free urine was recovered with an efficiency of 90-98%, but somewhat less reproducibly (CV, 12.8%). No interfering substances were found in normal urines. Between 35-98% of a single therapeutic (10 mg) dose given to hyperkinetic children could be recovered from the urine collected during the 6 h immediately after the dose. Only a small proportion was excreted as the unchanged drug (0.8-11.0%), the remainder being excreted as ritalinic acid.

Download Full-text