Liquid chromatography/positive ion electrospray tandem mass spectrometry method for the quantification of hydrochloride meptazinol in human plasma: application to a pharmacokinetic study.

A robust and validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method with positive electrospray ionization (ESI) was developed for the determination of hydrochloride meptazinol in human plasma. After liquid-liquid extraction of 200mul of human plasma, HPLC separation was achieved on a Thermo Hypurity Cyano column, using acetonitrile:ammonium formate (50mM, aq) (70:30, v/v) as the mobile phase. The mass spectrometer was operated in multiple reaction monitoring (MRM) mode using the transition m/z 234-->234 for meptazinol and m/z 152-->110 for the IS (acetaminophen), respectively. The calibration curves were linear over the range of 0.2925-292.5ng/ml, with the limit of quantification (LOQ) 0.2925ng/ml. The mean absolute recovery of hydrochloride meptazinol was more than 70.21%. Intra- and inter-day precisions were less than 9.05% and 12.89%, respectively. And the accuracy was within -2.99% to 4.96%. This method was applied to a pharmacokinetic study of hydrochloride meptazinol tablets in healthy Chinese volunteers.

Determination of the stereoselective aspects in in-vitro and in-vivo metabolism of the analgesic meptazinol by high-performance liquid chromatography.

A reversed-phase high-performance liquid chromatographic method to separate meptazinol and its phase I metabolites has been developed using a LiChrosper 100 CN column and a mobile phase of trimethylammoniumacetate buffer (pH 5.5)-acetonitrile-methanol. Quantification of meptazinol and N-desmethylmeptazinol in biological samples was achieved by extraction with organic solvents and chromatographic analysis (detection limit 0.4 and 0.25 micrograms/ml, respectively). Afterwards the enantiomeric ratio of the two compounds was determined on a Chiral AGP column with a mobile phase of phosphate buffer (pH 7.0)-acetonitrile (alpha = 1.29 and 1.49, respectively). In-vitro metabolism data after incubation of the racemic compound and the enantiomers with liver supernatant and microsomes of different species are presented. Finally urinary data of two volunteers after oral application of the racemic drug were determined.

Quantitative aspects of the urinary excretion of meptazinol and its metabolites in human volunteers.

1. The urinary excretion of meptazinol and its metabolites has been studied in five healthy human volunteers following oral administration of 200 mg of the 3H-labelled drug. 2. Meptazinol was well absorbed, with 90% of the radioactivity excreted in the urine; elimination of drug-related material took place rapidly. 3. Metabolism was extensive, no unchanged material being detected in the urine. Following selective enzymic hydrolysis the major metabolites were identified as glucuronide and sulphate conjugates of the parent drug present in an approximate ratio of 4:1. 4. A number of minor metabolites, also present in conjugated form, were tentatively identified.