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[Determination of Mephenytoin and 4'-hydroxymephenytoin in Urine by High Performance Liquid Chromatography]

Z R Ruan, Y S Cheng, D Y Ding

Yao Xue Xue Bao. 1994;29(8):624-8.

PMID: 7985520

Abstract:

A simple, sensitive and reproducible HPLC assay is described for the determination of mephenytoin and 4'-hydroxymephenytoin in human urine. Phenobarbital was used as an internal standard. The compounds were separated on a mu-Bondapack RP-C18 column using a mobile phase of acetonitrile-distilled water (40:60, v/v). The temperature of the column was maintained at 50 degrees C, and the UV detector was set at 210 nm. Calibration curves in the range 0.05-1.00 micrograms/ml for mephenytoin and 0.5-100.0 micrograms/ml for 4'-hydroxymephenytoin were linear (r = 0.9998 and r = 0.9992, respectively). The average recovery was 95.10 +/- 2.95%, and the relative standard deviation within day and day to day was less than 10%. The detection limit for mephenytoin was 25 ng/ml and 4'-hydroxymephenytoin was 50 ng/ml. The method was used to study the metabolism of S-mephenytoin 4'-hydroxylatoin in 10 healthy volunteers. The 12 h urinary metabolic ratio (MR) and hydroxylation index (HI) were calculated to express interindividual variation in metabolism. Two of them exhibited defective 4'-hydroxylation of S-mephenytoin as poor metabolizers (HI: 1349.18 and 409.57; MR: 105.29 and 8.52). In the remaining 8 subjects, the HI ranged from 1.68 to 6.71 and the MR ranged from 0.002 to 0.015, as extensive metabolizers of S-mephenytoin.

Chemicals Related in the Paper:

Catalog Number Product Name Structure CAS Number Price
AP61837658 4-Hydroxymephenytoin 4-Hydroxymephenytoin 61837-65-8 Price
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