A rapid liquid chromatography/tandem mass spectrometry method for simultaneous determination of levodopa, carbidopa, entacapone and their six related compounds in film‐coated tablets

Abstract

Rationale:A liquid chromatography/tandem mass spectrometry (LC/MS/MS) method has been developed and validated to determine levodopa, carbidopa, entacapone, and corresponding six related substanceslevodopa impurity B, levodopa impurity C, methyldopa, methylcarbidopa, entacapone impurity C, and entacapone impurity Ain film-coated tablets for the first time.Methods: Chromatographic separation was achieved with a gradient elution by using a C18 column, a mobile phase containing 0.5% formic acid in water and 0.5% formic acid in methanol. The mobile phase flow rate was 0.5 mL min −1 . The UV detector was set at 280 nm and the triple quadrupole mass spectrometer was used in multiple reaction monitoring (MRM) mode. Results:The limit of detection (LOD) and limit of quantification (LOQ) results were 1.3 and 3.94 ng mL −1 for levodopa impurity B; 5.26 and 15.9 ng mL −1 for levodopa impurity C; 0.833 and 2.53 ng mL −1 for methyldopa; 3.31 and 10.0 ng mL −1 for methylcarbidopa; 1.67 and 5.06 ng mL −1 for entacapone impurity C; and 0.61 and 1.86 ng mL −1 for entacapone impurity A. Conclusions:The method was rapid, linear, accurate, and reproducible. The LC/MS/MS method that was developed to determine the related substances and assay of levodopa, carbidopa, and entacapone can be used to evaluate the quality of regular samples in the pharmaceutical industry. It can be also used to test the stability of samples.

A voltammetric method coupled with chemometrics for determination of a ternary antiparkinson mixture in its dosage form: greenness assessment

“…Various analytical methods have been developed for the quantitative determination of LD, CD, and ENT simultaneously, separately, or in combination with other medications. These techniques include Liquid Chromatography with tandem mass spectrometry (LC-MS-MS) [ 7 – 9 ], High Performance Liquid Chromatography (HPLC) [ 10 – 14 ], Thin Layer Chromatography [ 15 , 16 ], spectrophotometry [ 17 – 23 ], capillary electrophoresis [ 24 , 25 ], and electrochemical methods [ 26 – 31 ]. The majority of chromatographic techniques need high purity solvents including organic solvents, high-cost instrument operation, experienced personnel, long analysis time and sample pretreatment steps [ 32 ].…”

Development and Validation of a New LC-MS/MS Bioanalytical Method for the Simultaneous Determination of Levodopa, Levodopa Methyl Ester, and Carbidopa in Human Plasma Samples

“…Although useful for its purpose, the main limitation of this methodology was the ability to evaluate the sole L-DOPA plasma concentration. Various LC-MS/MS methods were developed to monitor L-DOPA and carbidopa in human plasma [27][28][29][30][31][32][33], but to date, no method was found in the scientific literature for the monitoring of LDME in LC-MS/MS.…”

Application of a Tetraamino Cobalt(II) Phthalocyanine Modified Screen Printed Carbon Electrode for the Sensitive Electrochemical Determination of L‐Dopa in Pharmaceutical and Biological Samples

“…Various methods are currently used for the determination of L‐dopa, such as high performance liquid chromatography [5–7], liquid chromatography/tandem mass spectrometry [8], flow injection analysis [9, 10], spectrophotometry [11–13], a fluorescence method [14] and other techniques that can be used for effective L‐dopa detection, but some of these techniques need expensive equipment, complex experimental procedures and long analysis time. On the other hand, electrochemical methods are preferred due to their simplicity, high sensitivity, very good selectivity and low cost.…”