Abstract
Reactions between active drug substances and excipients are of interest in the drug formulation process should be checked for the interactions during the storage conditions. Some excipients react with certain chemical groups in drug substances which will form new impurities in the finished product formulations. In the present paper transesterification reaction of methylphenidate with glycerin to form different structural isomeric products was described. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. Stability samples were analyzed and observed that about ~0.6% of the Methylphenidate content was transformed into methylphenidate-glycerin isomers within 3 Months at 40°C/75% RH and 18 Months at 25°C/60% RH conditions. Analysis of two lots of marketed preparations having expiry dates in 2012 and 2013 showed content of the Methylphenidate esters corresponding to ~0.6% of the declared Methylphenidate content. The samples of this impurity were investigated by HPLC, UPLC-MS/MS to generate the mechanism of the impurity formation.
Highlights
Methylphenidate (Figure 1) is a central nervous system (CNS) stimulant of the phenethylamine and piperidine classes that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy
The objective of the present research article is to give a procedural identification of these unknown peaks and its formation, stability and toxicity in the Methylphenidate oral solution using HPLC, LC-MS/MS
LC-MS/MS system (Acquity UPLC coupled with TQD mass spectrometer with empower software, Waters Corporation, Milford, USA) was used for the identification of unknown compounds formed during forced degradation and stability testing studies
Summary
Methylphenidate (Figure 1) (trade names Concerta, Methylin, Medikinet, Ritalin, Equasym XL, Quillivant XR, Metadate) is a central nervous system (CNS) stimulant of the phenethylamine and piperidine classes that is used in the treatment of attention deficit hyperactivity disorder (ADHD) and narcolepsy. Methylphenidate oral solution shows two unknown impurities in the related compound method which is more than the identification threshold as per the ICH guidelines. These impurities identified in forced degradation studies, excipient compatibility studies and stability analysis of the finished product. The objective of the present research article is to give a procedural identification of these unknown peaks and its formation, stability and toxicity in the Methylphenidate oral solution using HPLC, LC-MS/MS. The formation of these impurities is less than one percent, so that the isolation and characterization of these impurities was not feasible.
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