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N Ratnaraj

Publications and source records attributed to N Ratnaraj.

22 records · Page 2Linked to original sources

Routine monitoring of carbamazepine and carbamazepine-10,11-epoxide in plasma by high-performance liquid chromatography using 10-methoxycarbamazepine as internal standard.

Carbamazepine and carbamazepine-10,11-epoxide were separated by high-performance liquid chromatography (HPLC) with acetonitrile-water as mobile phase, and detection was effected by UV absorption at 215 nm with a total retention time of less than 10 min. Plasma samples were extracted with dichloromethane and 4 M sodium hydroxide, and 10-methoxy-carbamazepine was added as internal standard. Other commonly used anticonvulsant drugs present in plasma showed no significant interference. The within-batch coefficient of variation for carbamazepine was 4.9% and carbamazepine-10,11-epoxide 5.9%. Between-batch coefficients of variation were 3.7% and 5.3%, respectively. Mean recovery for carbamazepine was 100.2% and for carbamazepine-10,11-epoxide 100.6%. This HPLC method was compared with both an enzyme immunoassay procedure (EMIT) and a gas-liquid chromatographic (GLC) method. Correlation coefficient between HPLC/EMIT for carbamazepine was 0.983, HPLC/GLC carbamazepine 0.988 and HPLC/GLC carbamazepine-10,11-epoxide 0.981.

Carbamazepine↗

Valproic acid estimation by enzyme immunoassay.

Blood samples from patients on long-term sodium valproate (Epilim) therapy were analysed for valproic acid by two procedures, enzyme immunoassay (EMIT) and gas-liquid chromatography (GLC). A critical evaluation of the effects of anticoagulants added to specimens was performed in addition to studies on reagent specificity, accuracy, and precision. EMIT valproic acid reagent showed high specificity, and there was a good correlation between results obtained by EMIT and GLC over a wide range of concentrations. The accuracy and precision of EMIT assay was good over the therapeutic range of valproic acid. The presence of the anticoagulant EDTA or of fluoride/oxalate produced a bias towards high results for valproic acid as compared with those obtained from the analysis of serum.

Chromatography, Gas↗

Blood and cerebrospinal fluid pharmacokinetics of primidone and its primary pharmacologically active metabolites, phenobarbital and phenylethylmalonamide in the rat.

Primidone is a clinically useful antiepileptic drug that is metabolised to two pharmacologically active metabolites phenobarbital and phenylethylmalonamide. As data on the inter-relationship between the systemic and central nervous system pharmacokinetics of primidone and its metabolites are sparse, we have investigated their temporal inter-relationship using a freely behaving rat model which allows repeated sampling of blood (100 microl) and cerebrospinal fluid (CSF; 20 microl). After administration, by intraperitoneal injection (50, 100 or 200 mg/kg), primidone rapidly appeared in both serum (Tmax mean range 1.5-2.5 h) and CSF (Tmax mean range 2.0-3.5 h), suggesting ready penetration of the blood-brain-barrier. This was also the case for phenylethylmalonamide and phenobarbital but peak concentration occurred later. Primidone, phenylethylmalonamide and phenobarbital concentrations rose linearly and dose-dependently in both serum and CSF. The mean free fraction (free/total concentration ratio) for primidone, phenylethylmalonamide and phenobarbital was 0.86, 0.97 and 0.88, respectively, and, as their respective mean CSF/serum ratio values were 0.73, 1.06 and 0.65, it would suggest that equilibration between the blood and CSF compartments is rapid. CSF mean t(1/2) values for primidone, phenylethylmalonamide and phenobarbital were similar to those of sera and essentially paralleled the pattern seen in sera.

Animals↗