Monitoring of carbamazepine and carbamazepine 10,11-epoxide in breast milk and plasma by high-performance liquid chromatography.
A high-performance liquid chromatographic method was developed for the measurement of carbamazepine (CBZ) and carbamazepine 10,11-epoxide (CBZE) in human breast milk and plasma. The method involves rapid C18 solid-phase extraction of CBZ and CBZE. Chromatographic separation was achieved with a reversed-phase C8 column using a mobile phase of potassium dihydrogenphosphate (pH 2.5) and acetonitrile (67:33 v/v), with ultraviolet detection at 254 nm. 2-Methyl CBZ was used as the internal standard. Determination of both CBZ and CBZE was possible in the range of 0.01-6.0 mg/L and 0.02-6.0 mg/L in milk and plasma, respectively. The recoveries of CBZ and CBZE added to the milk and plasma were 90.6-98.0% and 88.9-104.0%, respectively, with coefficients of variation less than 8.3% and 10.5%, respectively. The method has been used for drug level monitoring in milk and plasma samples obtained from CBZ-treated patients. The mean (SD) levels for CBZ in milk and plasma samples were 3.50 (0.4) mg/L and 6.18 (2.9) mg/L, and for CBZE were 1.28 (0.3) mg/L and 1.85 (1.0) mg/L, respectively. The mean (SD) milk/plasma ratios of CBZ and CBZE were 0.64 (0.2) and 0.79 (0.3), respectively. The milk/plasma ratio of CBZE was slightly higher than that of CBZ.
Shimoyama
R
R
Department of Pharmacy, Hirosaki University Hospital, Japan.
Ohkubo
T
T
Sugawara
K
K
D000328:Adult; D000927:Anticonvulsants / Q000032:analysis* / Q000097:blood; D002138:Calibration; D002220:Carbamazepine / Q000031:analogs & derivatives* / Q000032:analysis* / Q000097:blood; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D005260:Female; D006801:Humans; D007564:Japan; D007774:Lactation; D008895:Milk, Human / Q000737:chemistry*; D015203:Reproducibility of Results; D013997:Time Factors
D000927:Anticonvulsants; D002220:Carbamazepine; C012227:carbamazepine epoxide