Abstract
A simple, highly sensitive, precise and accurate high-performance liquid chromatographic (LCMSMS) method with mass detection was developed and validated for the rapid quantification of metaxalone (CAS Registry No, 1665- 48-1) in rat plasma samples. The chromatographic separation was achieved with a reverse phase column Agilent XDB C18 (4.6×100 mm, 5μ) and the mobile phase consisted of methanol and 5 mm ammonium acetate buffer (80:20 v/v) as eluent, at a flow rate of 0.6 mL/min. Phenytoin (CAS Registry no, 57-41-0) was used as an internal standard. The effluence was ionized by positive electrospray ionization and measured by mass spectrometry. The retention time of metaxalone and phenytoin were found to be 1.60 and 1.83 min respectively. The calibration curve was linear (r2 > or = 0.99) ranging from 0.98 to 998 ng/ml and the lower limit of quantification was 0.98 ng/mL. Interday and Intraday precision were lower than 5% (CV) and accuracy ranged from 90 to 110% in terms of percent accuracy. Mean extraction recovery was found to be above 82%. The method was successfully demonstrated for evaluation of pharmacokinetic profile of metaxalone in male Sprague dawley rats and validated for excellent selectivity, accuracy, precision, recovery and stability.
Highlights
Metaxalone has the molecular formula C12H15NO3 and chemical name 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone) with a molecular mass of 221.26 g/mol and absorption maxima around 280 nm
The drug is not recommended for patients with significant renal, hepatic disease and drug induced anaemias [9]
LC-MS/MS analysis was performed on Applied Biosystems/MDS SCIEX API 4000 LC-MS/MS triple quadrupole mass spectrometry with electrospray ionization (ESI) source and is enhanced by the high degree of automation and data processing capabilities of Analyst software supplied by Labindia Instrument Pvt
Summary
Metaxalone has the molecular formula C12H15NO3 and chemical name 5-[(3,5-dimethylphenoxy)methyl]-2-oxazolidinone) with a molecular mass of 221.26 g/mol and absorption maxima around 280 nm. Metaxalone belong to the BCS class II of centrally acting skeletal muscle relaxant drug with antispasmodic effect [1]. Metaxalone belongs to non benzodiazepine antispasmodics with a structure similar to mephenaxalone nucleus [2]. The mode of action of the metaxalone is clearly unknown but hypothesized as CNS depressant drug which causes skeletal muscle relaxation and sedation [4]. It acts through inhibiting interneuronal activity and blocking polysynaptic reflex pathways at spinal cord and at descending reticular formation in brain but leaving monosynaptic pathways intact like other similar class of skeletal muscle relaxants [5,6]. Metaxalone directly does not cause any relaxant effect on tense skeletal muscles or on the contractile mechanism of striated muscle, the motor end plate or the nerve fiber in humans
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