| Title | Comparison of fused-core and conventional particle size columns by LC-MS/MS and UV: Application to pharmacokinetic study. | | Author(s) | Song W, Pabbisetty D, Groeber EA, Steenwyk RC, Fast DM | | Institution | Pharmacokinetics, Dynamics and Metabolism, Pfizer Global R&D, Groton, CT 06340, USA. | | Source | J Pharm Biomed Anal 2009 May 22. | | Abstract | The chromatographic performance of fused-core (superficially porous) HPLC packing materials was compared with conventional fully porous particle materials for LC-MS/MS analysis of two pharmaceuticals in rat plasma. Two commercially available antidepressants, imipramine and desipramine, were assayed using a conventional analytical C(18) column (5mum, 2.0mmx30mm) and a fused-core C(18) column (2.7mum, 2.1mmx30mm). Retention time, column efficiency, pressure drop, resolution, and loading capacity were compared under the same operating conditions. The fused-core column demonstrated reduced assay time by 34% and 2-3-fold increased efficiency (N). Loading capacity up to 25mul of extract injected on column showed no peak distortion. The registered back-pressure from a flow rate of 1.0ml/min did not exceed 3400psi making it compatible with standard HPLC equipment (typically rated to 6000psi). Two mobile phases were examined, and morpholine as an organic base modifier yielded a 2-5-fold increase in S/N near the limit of detection over triethylamine. The 2.7mum fused-core column was applied to the analysis of imipramine and desipramine in extracted, protein precipitated rat plasma by LC-MS/MS. The calibration curves were linear in the concentration range of 0.5-1000ng/ml for both imipramine and desipramine. Intra-run precisions (%CV) and accuracies (%bias) were within +/-7.8% and +/-7.3% at three QC levels and within 14.7% and 14.4% at the LOQ level for both analytes. Following a single method qualification run, the method was applied to the quantitation of pharmacokinetic study samples after oral administration of imipramine to male rats. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19540084 |
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