IMPROVED METHOD FOR THE MEASUREMENT OF CIMETIDINE IN HUMAN-SERUM BY REVERSE-PHASE HIGH-PRESSURE LIQUID-CHROMATOGRAPHY
- 1 January 1981
- journal article
- research article
- Vol. 97 (4), 545-550
Abstract
An improved method for the measurement of cimetidine in human serum by reverse-phase HPLC [high pressure liquid chromatography] was developed. The assay involves the addition of the following to 1.0 ml of serum: 5 ml of ethyl acetate/isopropanol (96:4 by volume), 0.1 ml of 5N NaOH and 0.1 ml of the internal standard, N-cyano-N''-methyl-N"-[3-(4-imidazolyl)propyl]-guanidine, which is a close structural analog of cimetidine. The extracted cimetidine is quantitated with a HPLC containing a reverse-phase column and a variable-wavelength UV detector (228 nm). The mobile phase consists of methanol in 5 mM K2HPO4 (adjusted to pH 2.8) as a 10:90 mixture by volume. At a flow rate of 2 ml/min, the retention times for the internal standard and cimetidine are 2.8 and 6.2 min, respectively. The standard curve for cimetidine is linear from 0.1 to at least 4.0 .mu.g/ml in serum. The CV [coefficient of variation] of this assay for cimetidine, obtained from analysis of 6 replicate samples of a 1.0 .mu.g/ml serum pool, is 2%. The CV of this method obtained from the daily analysis (no. = 12) of the 1.0 .mu.g/ml cimetidine standard, is 3% and that from the 0.5 .mu.g/ml standard is 5%. Cimetidine was stable in refrigerated or frozen serum for 1 mo. and in whole blood for 24 h either at room temperature or refrigerated. In the serum from 13 patients receiving cimetidine therapy, the trough cimetidine levels varied from < 0.1 to 2.7 mg/ml.This publication has 7 references indexed in Scilit:
- Dose and serum concentration relationships in cimetidine-associated mental confusionGastroenterology, 1980
- Pharmacokinetics and Bioavailability of Cimetidine in Gastric and Duodenal Ulcer PatientsClinical Pharmacokinetics, 1980
- Cimetidine assay in human plasma by liquid chromatographyJournal of Chromatography B: Biomedical Sciences and Applications, 1979
- PHARMACOKINETIC AND CLINICAL STUDIES IN PATIENTS WITH CIMETIDINE-ASSOCIATED MENTAL CONFUSIONThe Lancet, 1979
- High-pressure liquid chromatographic determination of cimetidine sulphoxide in human blood and urineJournal of Chromatography B: Biomedical Sciences and Applications, 1978
- High-Pressure Liquid Chromatographic Analysis of Cimetidine, a Histamine H2-Heceptor Antagonist, in Blood and UrineJournal of Pharmaceutical Sciences, 1977
- PLASMA-PROTEIN BINDING OF BASIC DRUGS .1. SELECTIVE DISPLACEMENT FROM ALPHA1-ACID GLYCOPROTEIN BY TRIS(2-BUTOXYETHYL) PHOSPHATE1977