Pharmacokinetic Study Of The Compound Preparation Of Carisoprodol

Objectives The LC/MS/MS method for the simultaneous determination of carisoprodol and meprobamate in human plasma was developed and validated. A selective HPLC-UV method for determination of salicylic acid in human plasma was developed. The two methods were successfully used in the clinical pharmacokinetic study of carisoprodol tablets and carisoprodol and aspirin tablets. Methods To detect the carisoprodol and meprobamate, a small volume of plasma (100 μL) spiked with the analytes and the internal standard was processed using liquid-liquid extraction. The extract was chromatographed on a Zorbax SB C₁₈ column. The mobile phase, consisted of acetomtrile-water-formic acid (80: 20: 0.2, v/v/v), was delivered at a flow rate of 0.60 mL/min. A tandem mass spectrometer equipped with atmospheric pressure chemical ionization source was used as the detector and was operated in the positive ion mode. Detection of the ions was performed in the selected reaction monitoring (SRM) mode by monitoring the transitions of m/z 261 → m/z 176 for carisoprodol, m/z 219 → m/z 158 for meprobamate and m/z 230 → m/z 121 for osalmide (IS), respectively. To detect the salicylic acid, a small volume of plasma spiked with the analytes and the internal standard was deproteinated by acetonitrile, and then separated on a Diamonsil C₁₈ column. The mobile phase, consisted of acetonitrile-water-phosphoric acid (110: 90: 0.25, v/v/v), was delivered at a flow rate of 1.2 mL/min. Lomoxicam was used as the internal standard. The wavelength was at 299 nm. Results The assay was reproducible and linear for both carisoprodol and meprobamate in the range of 0.0065-10.0 μg/mL. The lower limit of quantification of the analytes was 0.0065 μg/mL. The intra- and inter-run precisions were less than 9.0%, determined from QC samples for carisoprodol or meprobamate, and accuracy were within ± 4.6%. When the salicylic acid was detected, the assay was reproducible and linear for salicylic acid in the range of 0.40-80.0 μg/mL. The lower limit of quantification of the analytes was 0.40 ug/mL. The intra- and inter-run precisions were less than 9.5%, determined from QC samples for salicylic acid, and accuracy were within ±2.6%.