In Vitro Analysis of N-Nitrosodimethylamine (NDMA) Formation From Ranitidine Under Simulated Gastrointestinal Conditions.

Importance: A publication reported that N-nitrosodimethylamine (NDMA), a probable human carcinogen, was formed when ranitidine and nitrite were added to simulated gastric fluid. However, the nitrite concentrations used were greater than the range detected in acidic gastric fluid in prior clinical studies. Objective: To characterize NDMA formation following the addition of ranitidine to simulated gastric fluid using combinations of fluid volume, pH levels, and nitrite concentrations, including physiologic levels. Design, Setting, and Participants: One 150-mg ranitidine tablet was added to 50 or 250 mL of simulated gastric fluid with a range of nitrite concentrations from the upper range of physiologic (100 µmol/L) to higher concentrations (10 000 µmol/L) with a range of pH levels. NDMA amounts were assessed with a liquid chromatography-mass spectrometry method. Main Outcomes and Measures: NDMA detected in simulated gastric fluid 2 hours after adding ranitidine. Results: At a supraphysiologic nitrite concentration (ie, 10 000 µmol/L), the mean (SD) amount of NDMA detected in 50 mL simulated gastric fluid 2 hours after adding ranitidine increased from 222 (12) ng at pH 5 to 11 822 (434) ng at pH 1.2. Subsequent experiments with 50 mL of simulated gastric fluid at pH 1.2 with no added nitrite detected a mean (SD) of 22 (2) ng of NDMA, which is the background amount present in the ranitidine tablets. Similarly, at the upper range of physiologic nitrite (ie, 100 µmol/L) or at nitrite concentrations as much as 50-fold greater (1000 or 5000 µmol/L) only background mean (SD) amounts of NDMA were observed (21 [3] ng, 24 [2] ng, or 24 [3] ng, respectively). With 250 mL of simulated gastric fluid, no NDMA was detected at the upper physiologic range (100 µmol/L) or 10-fold physiologic (1000 µmol/L) nitrite concentrations, while NDMA was detected (mean [SD] level, 7353 [183] ng) at a 50-fold physiologic nitrite concentration (5000 µmol/L). Conclusions and Relevance: In this in vitro study of ranitidine tablets added to simulated gastric fluid with different nitrite concentrations, ranitidine conversion to NDMA was not detected until nitrite was 5000 µmol/L, which is 50-fold greater than the upper range of physiologic gastric nitrite concentrations at acidic pH. These findings suggest that ranitidine is not converted to NDMA in gastric fluid at physiologic conditions.

Pharmacokinetics and efficacy of intravenous famotidine in adult cattle.

BACKGROUND: Abomasal ulceration is recognized in neonatal and adult cattle, but research regarding treatment is limited. Histamine-2 receptor antagonists (H2 RA), such as famotidine, are used clinically with little evidence-based research about efficacy in adult cattle. HYPOTHESIS AND OBJECTIVES: Intravenous famotidine administered at 0.4 mg/kg will increase the pH of abomasal outflow digesta compared to saline control in adult cattle. The objectives were to assess the effect of famotidine, administered as a single dose and as multiple doses, on abomasal outflow fluid pH in adult cattle. A third objective was to describe the pharmacokinetic parameters of IV famotidine in cattle. ANIMALS: Four clinically healthy adult Angus-cross steers previously fitted with duodenal cannulae placed orad to the biliary and pancreatic ducts. METHODS: Randomized, 2-way cross-over clinical trial. Steers received IV famotidine (0.4 mg/kg) as a single and 3-dose regimen (every 8 hours) versus saline control. Blood for analysis of serum famotidine concentration was collected intermittently for 12 hours, and abomasal outflow fluid pH was measured at intervals for a 24-hour period. After a 34-hour washout period, the opposite treatments were administered and the sampling repeated. RESULTS: Abomasal outflow fluid pH was higher in steers treated with famotidine for up to 4 hours after a single dose but the effect decreased with subsequent doses. The median (range) elimination half-life was 3.33 (3.21-3.54) hours. CONCLUSIONS AND CLINICAL IMPORTANCE: Famotidine may be useful for treatment or prevention of abomasal ulceration in adult cattle, but the duration of effect may decrease with time.

An Efficient Ion-Pair Liquid Chromatographic Method for the Determination of Some H2 Receptor Antagonists.

A simple, efficient and reliable ion-pair chromatography (IPC) method was developed and validated for the determination of some H2 receptor antagonists including ranitidine (RAN), nizatidine (NIZ) and famotidine (FAM). The use of IPC separations provided improved peak resolution with good peak shape in short analysis time and augmented method selectivity compared with the frequently used RP-C18 methods. A simple isocratic mode with mobile phase containing acetonitrile and 20 mM acetate buffer (50 : 50, v/v) containing 20 mM sodium dodecyl sulfate was used for separation. The flow rate was set at 1.0 mL min(-1), and the effluent was monitored by UV detector at 280 nm FAM and 320 nm for NIZ and RAN. The method was validated in accordance with International Conference on Harmonization guidelines and shown to be suitable for intended applications. The limits of detections and quantitations were 0.008-0.011 and 0.025-0.033 µg mL(-1), respectively. The proposed IPC method was successfully applied for the determination of pharmaceutical dosage forms without prior need for separation. Additionally, the developed method was applied for the determination of RAN in rabbit plasma using NIZ as the internal standard. The method entailed direct injection of the plasma samples after deproteination using methanol. Finally, the proposed IPC method was applied successfully in a pharmacokinetic study for RAN in rabbits after a single oral dose of RAN.

Development and validation of a sensitive LC-MS/MS assay for the quantification of nizatidine in human plasma and urine and its application to pharmacokinetic study.

We developed and validated a high performance liquid chromatographic method coupled with triple quadrupole mass spectrometry for analysis of nizatidine in human plasma and urine. The biological samples were precipitated with methanol before separation on an Agilent Eclipse Plus C18 column (100mm×46mm, 5µm) with a mixture of methanol and water (95:5, plus 5mM ammonium formate) as the mobile phase at 0.5mL/min. Detection was performed using multiple reaction monitoring modes via electrospray ionization (ESI) at m/z 332.1→155.1 (for nizatidine) and m/z 335.1→155.1 (for [(2)H3]-nizatidine, the internal standard). The linear response range was 5-2000ng/mL and 0.5-80µg/mL for human plasma and urine, with the lower limits of quantification of 5ng/mL and 0.5µg/mL, respectively. The method was validated according to the biological method validation guidelines of the Food and Drug Administration and proved acceptable. This newly developed analytical method was successfully applied in a pharmacokinetic study following single oral administration of a 150mg nizatidine capsule in to 16 healthy Chinese subjects. Maximum and endpoint concentrations in plasma and urine were quantifiable, suggesting our method is appropriate for routine pharmacokinetic analysis.

Spectrofluorimetric analysis of famotidine in pharmaceutical preparations and biological fluids by derivatization with benzoin.

A sensitive and simple spectrofluorimetric method has been developed for the analysis of famotidine, from pharmaceutical preparations and biological fluids after derivatization with benzoin. The reaction was carried out in alkaline medium with measurement of fluorescence intensity at 446 nm with excitation wavelength at 286 nm. Linear calibration was obtained with 0.5-15 µg/ml with coefficient of determination (r(2)) 0.997. The factors affecting the fluorescence intensity were optimized. The pharmaceutical additives and amino acid did not interfere in the determination. The mean percentage recovery (n=4) calculated by standard addition from pharmaceutical preparation was 94.8-98.2% with relative standard deviation (RSD) 1.56-3.34% and recovery from deproteinized spiked serum and urine of healthy volunteers was 98.6-98.9% and 98.0-98.4% with RSD 0.34-0.84% and 0.29-0.87% respectively.

Pharmacokinetics and pharmacodynamics of famotidine and ranitidine in critically ill children.

To characterize and compare acid suppression (pharmacodynamics) and pharmacokinetics of IV famotidine and ranitidine in critically ill children at risk for stress gastritis. Single-blind, randomized study in PICU patients 6 months to 18 years requiring mechanical ventilation with continuous gastric pH monitoring, randomized to IV famotidine 12 mg/m(2) or ranitidine 60 mg/m(2) when gastric pH < 4.0 >1 hour with serial blood sampling following first dose. Twenty-four children randomized to either famotidine (n = 12) or ranitidine (n = 12). Sixteen out of twenty-four completed both PK and PD study arms (7/12 famotidine; 4.7 ± 3.4 years; 9/12 ranitidine; 6.6 ± 4.7 years; p = 0.38). Time to gastric pH 4.0 and total time pH above 4.0 similar with no difference in pH at 6 and 12 hours (p > 0.2). No difference between drugs in clearance, volume of distribution and half-life (p > 0.05). Ratio of AUC pH to AUC drug concentration 0-12 hours after first dose was significantly greater for famotidine (0.06849 ± 0.01460 SD) than ranitidine (0.02453 ± 0.01448; p < 0.001) demonstrating greater potency of famotidine. pH lowering efficacy of both drugs is similar. Greater potency of famotidine may offer clinical advantage due to lower drug exposure and less frequent dosing to achieve same pH lowering effect.

HPLC fluorescence method for the determination of nizatidine in human plasma and its application to pharmacokinetic study.

A sensitive high-performance liquid chromatographic (HPLC) method was developed for the determination of nizatidine in human plasma. Nizatidine was derivatized by 4-fluoro-7-nitrobenzofurazan (NBD-F). Chromatographic separation was performed on a Inertsil C18 column (150 mm × 4.6 mm, 5 µm) using isocratic elution by a mobile phase consisting of methanol/water (55:45) at a flow rate of 1.2 mL/min. Amlodipine was used as the internal standard (IS). Fluorescence detector was used operated at 461 nm (excitation) and 517 nm (emission), respectively. The calibration curve was linear over the range of 50-2000 ng/mL. This method was successfully applied to a pharmacokinetic study after oral administration of a dose (150 mg) of nizatidine.

Pharmacokinetics of the H(2) blocker roxatidine acetate hydrochloride in pediatric patients, in comparison with healthy adult volunteers.

Clinical studies were conducted to investigate the pharmacokinetics of roxatidine acetate hydrochloride capsules (ALTAT(®) CAPSULES) in children. In a single-dose pharmacokinetic (PK) study in pediatric patients aged between 6 and 14 years with acid-related diseases, 37.5 mg or 75 mg roxatidine capsules were given orally, and blood samples were collected to determine the plasma roxatidine concentrations. Meanwhile, a single-dose PK study in healthy adult volunteers was newly conducted; subjects were given 37.5 mg, 75 mg or 150 mg roxatidine capsules. Differences were present between the PK parameters in pediatric patients and those in healthy adult volunteers. However, the CL/F and Vd/F adjusted by body surface area (BSA) or body weight (BW) were comparable. A close correlation of the C(max) and AUC(0-∞) to the dose per unit BSA (mg/m(2)) or BW (mg/kg) was also shown. In the multiple-dose study in pediatric patients, no roxatidine accumulation in plasma was observed, as was the case with a previous study in adults. These data show that the PK profile of roxatidine in pediatric patients is similar to the profile in healthy adult volunteers when adjusted by BSA or BW.

Development and validation of a dried blood spot LC-MS/MS assay to quantify ranitidine in paediatric samples.

A novel approach has been developed to determine ranitidine in paediatric samples using dried blood spots (DBS) on Guthrie cards (Whatman 903). A selective and sensitive HPLC-MS/MS assay has been developed and validated using small volumes of blood (30 µl). A 6 mm disc was punched from each DBS and extracted with methanolic solution of the internal standard (IS) nizatidine. This was further subjected to solid phase extraction (SPE), followed by reversed phase HPLC separation, using a XBridge™ C18 column and mobile phase 10 mM ammonium acetate/methanol (98:2 v/v) with a flow rate of 0.3 mL/min. This was combined with multiple reaction monitoring (MRM) mass detection using electrospray ionisation (ESI). The calibration curve for ranitidine was found linear over the range 10-500 ng/mL (r=0.996). The limit of quantification (LOQ) of the method was validated at 10 ng/mL. Accuracy and precision values for within and between days were <20% at the LOQ and <15% at all other concentrations. The validated DBS method was successfully applied to a clinical study employing 81 samples from 36 paediatric patients.

Development and validation of a RP-HPLC method for simultaneous estimation of naproxen and ranitidinehydrochloride.

A simple, specific and accurate reverse phase liquid chromatographic method has been developed for the simultaneous determination of naproxen and ranitidine HCl. Both the drugs are official with British Pharmacopoeia 2007, but do not involve simultaneous determination of naproxen and ranitidine HCl. The separation was carried out using 4.6 × 250 mm Symmetry Shield TM RP 18 with a particle diameter of 5 µm and mobile phase containing 0.1M orthophosphoric acid: methanol (35:65, pH 3.1) in isocratic mode. The flow rate was 1.00 ml/min and effluent was monitored at 240 nm. The retention times (average) of ranitidine HCl and naproxen were 2.36 min and 12.39 min, respectively. The linearity for naproxen and ranitidine HCl was in the range of 5-35 µg/ml and 1.5-12 µg/ml, respectively. The potencies of naproxen and ranitidine HCl were found 99.40 % and 99.48 %, respectively. The proposed method was validated and successfully applied to the estimation of naproxen and ranitidine HCl in newly formulated combined tablet and in plasma.

Simultaneous determination of metformin, cimetidine, famotidine, and ranitidine in human serum and dosage formulations using HPLC with UV detection.

A new, simple, and reliable reversed-phase high-performance liquid chromatographic method has been developed and validated for the simultaneous determination of metformin (Metf), cimetidine (Cimt), famotidine (Famt), and ranitidine (Rant) in their synthetic mixtures and tablet formulations. These drugs were separated on a Purospher Star RP18 endcapped (250 mm × 4.6 mm i.d.) column packed with 5-µm particles. The mobile phase, optimized through an experimental design, consisted of methanol-water-triethylamine (20:80:0.05), whose pH was adjusted to 3.0 with phosphoric acid (85%) pumped at a flow rate of 1.0 mL/min. UV detection was performed at 229 nm. The method was validated in the sample concentration range of 5-25 µg/mL for all the drugs, where it demonstrated good linearity with r = 0.9998, 0.9979, 0.9997, and 0.9987 (n = 6), respectively. For independent 100% level samples, the intra-day and inter-day precision was in the range i.e. < 2.0 for all the drugs. The method demonstrated robustness, resisting to small deliberate changes in pH, flow rate, and composition (organic:aqueous ratio) of the mobile phase. The limit of detection values were 0.071, 0.116, 0.134, and 0.110 µg/mL, while the limit of quantitation were 0.217, 0.352, 0.405, and 0.368 µg/mL for Metf, Cimt, Famt, and Rant, respectively. The applicability of the method was demonstrated by determining the drug content in pharmaceutical formulations, where it exhibited good performance.

A single LC-tandem mass spectrometry method for the simultaneous determination of four H2 antagonists in human plasma.

A sensitive and universal LC-MS/MS method for the simultaneous determination of famotidine, cimetidine, ranitidine and lafutidine in human plasma was presented. This is the first single LC-MS/MS method reported for the simultaneous analysis of these four H(2) antagonists in human plasma. Following liquid-liquid extraction with ethyl acetate, the separation was performed on an Agilent Zorbax SB-CN (150 mm x 2.1mm I.D., 5 microm) column using a mobile phase consisted of methanol:20 mM ammonium acetate (55:45, v/v). The total run time was 7 min per sample. Quantification was performed by electrospray ionization-triple quadrupole mass spectrometry by selected reaction monitoring (SRM) detection in the positive mode. All calibration curves showed good linear regression (r(2)>0.99) from 0.5 to 1000 ng/mL for famotidine and lafutidine, and 5-20,000 ng/mL for cimetidine and ranitidine. The method showed good precision and accuracy with overall intra- and inter-day variations of 1.37-9.29% and 3.51-9.40%, respectively. The assay was successfully applied to a bioequivalence study using ranitidine as the model compound.

Whole-body physiologically based pharmacokinetic population modelling of oral drug administration: inter-individual variability of cimetidine absorption.

OBJECTIVES: Inter-individual variability of gastrointestinal physiology and transit properties can greatly influence the pharmacokinetics of an orally administered drug in vivo. To predict the expected range of pharmacokinetic plasma concentrations after oral drug administration, a physiologically based pharmacokinetic population model for gastrointestinal transit and absorption was developed and evaluated. METHODS: Mean values and variability measures of model parameters affecting the rate and extent of cimetidine absorption, such as gastric emptying, intestinal transit times and effective surface area of the small intestine, were obtained from the literature. Various scenarios incorporating different extents of inter-individual physiological variability were simulated and the simulation results were compared with experimental human study data obtained after oral cimetidine administration of four different tablets with varying release kinetics. KEY FINDINGS: The inter-individual variability in effective surface area was the largest contributor to absorption variability. Based on in-vitro dissolution profiles, the mean plasma cimetidine concentration-time profiles as well as the inter-individual variability could be well described for three cimetidine formulations. In the case of the formulation with the slowest dissolution kinetic, model predictions on the basis of the in-vitro dissolution profile underestimated the plasma exposure. CONCLUSIONS: The model facilitates predictions of the inter-individual pharmacokinetic variability after oral drug administration for immediate and extended-release formulations of cimetidine, given reasonable in-vitro dissolution kinetics.

A tandem mass spectrometry assay for the simultaneous determination of acetaminophen, caffeine, phenytoin, ranitidine, and theophylline in small volume pediatric plasma specimens.

BACKGROUND: Acetaminophen, caffeine, phenytoin, ranitidine, and theophylline are widely used in pediatric pharmacotherapy, but only very limited information is available on the pharmacokinetics of these medications in premature neonates. As pharmacokinetic studies in this population are hampered by limitations in the number and volume of plasma samples, we developed an LC-MS/MS assay for the simultaneous determination of these medications in small volume human plasma specimens for pharmacokinetic evaluations in neonates. METHODS: Sample preparation was performed by protein precipitation with methanol after addition of internal standard to 50 microl of plasma specimen. After chromatographic separation on a C18 column using gradient elution, analytes were detected using a triple quadrupole mass spectrometer that was operated in positive ion mode with electrospray ionization. RESULTS: All 5 analytes could be simultaneously quantified in human plasma. The linear quantification range comprised 12.2 to 25,000 ng/ml for acetaminophen, phenytoin, and ranitidine, 24.4 to 25,000 ng/ml for theophylline, and 48.8 to 25,000 ng/ml for caffeine with accuracies ranging from 87.5 to 115.0%. The intra-day and inter-day precision (%CV) was between 2.8 and 11.8% and 4.5 and 13.5%, respectively. CONCLUSIONS: An accurate, sensitive, and reliable LC-MS/MS method was developed and validated to simultaneously quantify 5 drugs frequently used in neonatal pharmacotherapy.

Effect of Da-Cheng-Qi decoction on the pharmacokinetics of ranitidine in rats.

Da Cheng Qi decoction (DCQD) is composed of Dahuang, Houpu, Zhishi and Mangxiao. It is a formula created under the theory of Chinese medicine to purge the 'evil heat' in the gastrointestitinal tract, which arises from the ileus and acute pancreatitis. The present study was conducted to evaluate the herb-drug interaction between DCQD and ranitidine, which are often co-administered in clinical practice. Ranitidine was administered orally alone or together with DCQD to rats, and plasma ranitidine concentrations were measured by HPLC. Following oral administration, ranitidine plasma levels revealed curves characterized by peaks at 1.8 and 4.2 h corresponding to ranitidine alone and ranitidine with DCQD at mean concentrations of 16.315 and 1.455 microg/mL, respectively. After ranitidine was orally dosed alone or with DCQD, the half-lives were 1.787 and 3.758 h, while the area under the concentration-time curve (0-12 h) was 28.083 and 9.826 microg/L h, respectively, suggesting that DCQD might significantly affect the pharmacokinetics of ranitidine in rats. When physicians or pharmacists administer DCQD and ranitidine, they must make a careful effort to adjust the dosage of the drug and Chinese decoction, or avoid the herb-drug co-administration.

Leaky enteric coating on ranitidine hydrochloride beads: dissolution and prediction of plasma data.

The present research is based on the hypothesis that leaky enteric-coated pellets formulations are able to provide sustained input for drugs that have an absorption window, such as ranitidine hydrochloride, without jeopardizing their bioavailability. Leaky enteric-coated pellets formulations are defined as enteric-coated pellets that allow some of the drug to be released from the formulation in gastric fluid. Different approaches to making leaky enteric-coated pellets were investigated using extrusion-spheronization followed by spray coating. Leaky enteric coats were formulated using a commonly used enteric polymer, Eudragit L 30 D-55, combined with soluble compounds including lactose, PEG 8000 and surfactants (Span 60 (hydrophobic) or Tween 80 (hydrophilic)). The rate of drug release from the formulations in simulated gastric fluid can be tailored by varying the additive's amount or type. All leaky enteric-coated formulations studied completely released the drugs within 30 min after changing dissolution medium to phosphate buffer, pH 6. Predictions of plasma concentration-time profiles of the model drug ranitidine hydrochloride from leaky enteric-coated pellets in fasted conditions and from immediate-release formulations were performed using computer simulations. Simulation results are consistent with a hypothesis that leaky enteric-coated pellets formulations provide sustained input for drugs shown to have an absorption window without decreasing bioavailability. The sustained input results from the combined effects of the formulation and GI transit effects on pellets. The present research demonstrates a new application of knowledge about gastrointestinal transit effects on drug formulations. It also shows that enteric-coating polymers have new applications in areas other than the usual enteric-coated formulations. The hypothesis that a leaky enteric-coated pellets formulation may maintain or increase the bioavailability of drugs that have a window of absorption is still to be confirmed by further in vivo studies.

Sensitive determination of ranitidine in rabbit plasma by HPLC with fluorescence detection.

A sensitive high-performance liquid chromatographic method for determination of ranitidine (RAN) in rabbit plasma is described. The method is based on liquid-liquid extraction, labeling with dansyl chloride and monitoring with fluorescence detector at 338nm (ex)/523nm (em). Plasma samples were extracted with diethyl ether alkalinized with 1M sodium hydroxide. Ephedrine HCl (EPH-HCl) was used as internal standard. Both, RAN and EPH were completely derivatized after heating at 60 degrees C for 10min in sodium bicarbonate solution (pH 9.5). The derivatized samples were analyzed by HPLC using Agilent Zorbax Extended C18 column (150mmx4.6mm i.d.) and mobile phase consists of 48% acetonitrile and 52% sodium acetate solution (0.02M, pH 4.6). The linearity of the method was in the range of 0.025-10microg/ml. The limits of detection (LOD) and quantification (LOQ) were 7.5+/-0.18 and 22.5+/-0.12ng/ml, respectively. Ranitidine recovery was 97.5+/-1.1% (n=6; R.S.D.=1.8%). The method was applied on plasma collected from rabbits at different time intervals after oral administration of 5mg/kg ranitidine HCl.

Pharmacokinetic and pharmacodynamic properties of lafutidine after postprandial oral administration in healthy subjects: comparison with famotidine.

Lafutidine, a histamine H(2)-receptor antagonist, inhibits gastric acid secretion during the daytime, however, the relationship between the plasma concentration and the drug response remains unclear. The aim of this study was to compare the pharmacokinetic and pharmacodynamic properties of lafutidine and famotidine following postprandial oral administration. After a lafutidine tablet (10 mg), famotidine tablet (20 mg), or water only (control) was administered, blood samples were taken and intragastric pH was measured. The plasma concentrations of lafutidine and famotidine were determined by HPLC, and the median intragastric pH values per 30 min were used as the degrees of gastric acid suppression. Data were analyzed based on a one-compartment pharmacokinetic model and a sigmoid E(max) pharmacodynamic model. Lafutidine plasma concentrations rapidly increased after administration; famotidine required some time to increase the plasma concentrations, requiring an absorption lag time in the pharmacokinetic model. Between the plasma concentration and DeltapH (the difference in intragastric pH by the drug vs. control), lafutidine showed an anticlockwise hysteresis loop which indicated equilibration delay between the plasma concentration and effect site, requiring an effect site compartment in the pharmacodynamic model; famotidine showed more parallel relationship. These results indicated that the pharmacokinetic and pharmacodynamic properties of lafutidine after postprandial oral administration were different from those of famotidine at least 4.5 h after dosing.

Convenient and rapid determination of cimetidine in human plasma using perchloric acid-mediated plasma protein precipitation and high-performance liquid chromatography.

This study demonstrates the analysis of cimetidine in human plasma with HPLC using a simplified sample preparation by protein precipitation with perchloric acid. Plasma cimetidine concentration was determined by plotting peak height ratio of cimetidine to ranitidine (internal standard, IS) against cimetidine concentrations in plasma. The cimetidine and ranitidine peaks were completely separated and no interference from plasma was observed. The lower limit of quantification (LLOQ) of the method was established at 0.1 microg/mL with a precision of 4.3% and a relative error of 1.9%. The average analytical recovery was >90% over the range of cimetidine concentrations (0.1-15.0 microg/mL). The linearity of calibration curve was excellent (r(2) > 0.999). The within- and between-day precision and accuracy, expressed as the coefficients of variation and relative error, were found to be less than 5%. Compared with previously reported methods, the analytical technique for cimetidine determination in human plasma presented here demonstrates comparable accuracy and precision, an acceptable analysis time, shorter and simpler sample preparation, and a reduced need for complicated equipment. The method presented here is simple and rapid, and the precision and sensitivity are appropriate for the determination of cimetidine in plasma in pharmacokinetic studies.