Rapid analysis of ranitidine in biological fluids and determination of its erythrocyte partitioning

Mullersman, Gotelind; Derendorf, Hartmut

doi:10.1016/s0378-4347(00)83604-x

Cited by 21 publications

(7 citation statements)

References 11 publications

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“…Initially, our impres sion was assay interference with chloram phenicol. The HPLC method employed monitored peak absorbance of ranitidine at a wave length of 318 nm [16]. The peak UV absorbance of chloramphenicol in methanol is 274 nm [20].…”

Section: Resultsmentioning

confidence: 99%

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Pharmacokinetics of Ranitidine in Critically Ill Infants

et al. 1989

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The pharmacokinetic parameters of ranitidine were studied following administration of a single intravenous dose in 9 critically ill infants. Ranitidine disposition was best described by a biphasic elimination curve. For 8 patients, the mean values for T 1/2, apparent volume of distribution, and total body clearance were 2.09 h, 1.61 l/kg, and 13.93 ml/min/kg, respectively. Based on simulated steady-state concentration profiles, a dose of 0.7 mg/kg administered intravenously every 6 h should maintain serum levels above 40 ng/ml for 4.7 h of the dosing interval with a wide degree of variability.

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Section: Resultsmentioning

confidence: 99%

“…Plasma samples were thawed, extracted and as sayed for ranitidine using reverse-phase, high-perfor mance liquid chromatography (HPLC) [16]. The limit of sensitivity was 10ng/ml.…”

Section: Drug/data Analysismentioning

confidence: 99%

Pharmacokinetics of Ranitidine in Critically Ill Infants

et al. 1989

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“…(2) can be rearranged to Eqn. (3), where Q Total is the amount of compound in the whole blood. As depicted in Fig.…”

Section: Theorymentioning

confidence: 99%

“…In the ex vivo method, the compound is dosed to animals or humans and blood samples are serially taken for analysis using procedures similar to those in the in vitro method. In both methods, the drug concentrations in whole blood (or RBC) and plasma are measured separately using highperformance liquid chromatography (HPLC), 3 or, more recently, using liquid chromatography/tandem mass spectrometry (LC/MS/MS) methods. 4 However, even with the use of an LC/MS/MS method, RBC partitioning measurement is not straightforward.…”

mentioning

confidence: 99%

A novel liquid chromatography/tandem mass spectrometry based depletion method for measuring red blood cell partitioning of pharmaceutical compounds in drug discovery

Yang

et al. 2004

Rapid Comm Mass Spectrometry

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A novel liquid chromatography/tandem mass spectrometry (LC/MS/MS)-based depletion method for measuring compound partitioning between human plasma and red blood cells (RBC) in a drug discovery environment is presented. Conventionally, RBC partitioning is determined by separate measurements of drug concentrations in equilibrating plasma and whole blood or RBC using separate standards prepared in their respective matrices, i.e., in plasma and whole blood or RBC lysates. The process is very tedious, labor-intensive, and difficult to automate. In addition, interferences from the heme and other highly abundant cellular composites make the measurement of the drug concentration in whole blood or RBC inevitably variable even with a highly specific LC/MS/MS method. Therefore, there is an imminent need to develop a straightforward and fast method to assess the partitioning of drug-like compounds in RBC. This work describes an LC/MS/MS-based depletion assay that measures the compound concentration in plasma that has been equilibrating with RBC. Compounds were spiked into fresh human whole blood and plasma respectively to a final concentration of 500 nM. Both the spiked whole blood and plasma control were incubated at 37 degrees C for up to 60 min. During the time course, aliquots of plasma and whole blood from both incubation mixtures were sampled at 10 and 60 min. The whole blood samples were centrifuged to yield the plasma. The plasma samples from both incubations were extracted using a protein precipitation method, and analyzed using LC/MS/MS under the multiple-reaction monitoring (MRM) mode. The RBC partitioning ratio was calculated using the analyte peak area responses of the plasma samples through an equation deduced in this work. The method was first tested using two commercial compounds, phenoprobamate and acetazolamide, to determine the optimal incubation conditions and the concentration dependency of the assay. The assay reproducibility was also assessed by three inter-day assays for phenoprobamate. This method was further evaluated using 20 commercial compounds of different classes with a wide range of RBC partitioning coefficients and the results were compared with those reported in the literature. Excellent correlation (R2=0.9396) was found between the measured and literature values. In addition, several proprietary compounds were assayed using both the new and traditional methods and the measured partitioning ratios from the two methods are equivalent. The experiments in this work demonstrate that the LC/MS/MS-based depletion method can provide direct and accurate measurement of RBC partitioning for compounds in drug discovery.

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“…e molecular mass of ranitidine hydrochloride is 350.9 daltons (g/mol), and its molecular formula is C 13 ′ -methyl-nitro2-1,1-ethenodiamine. Ranitidine hydrochloride appears as a crystalline powder, practically odorless and white to light yellow.…”

Section: Introductionmentioning

confidence: 99%

Determination of Ranitidine in Human Plasma by SPE and ESI-LC-MS/MS for Use in Bioequivalence Studies

Bellorio

Alves

Filho

2013

ISRN Chromatography

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A method for determining ranitidine in human plasma by ESI-LC-MS/MS was validated, using propranolol as internal standard. e extraction method used was solid phase extraction (SPE). Chromatographic separation was performed in a Chromolith C18 (50 mm × 4.6 mm i.d.) analytical column, which provided good separation of ranitidine and propranolol peaks with an analysis time of 2.5 minutes. Extraction yields of 94.4% for ranitidine and 89.4% for the internal standard were obtained. e lower limit of quanti�cation (LLO�) was 3.00 ng/mL, and limit of detection (LOD) was 0.05 ng/mL, with linearity ranging from 3.00 to 500 ng/mL. e results, thus, showed that this method is suitable for application in bioequivalence studies of ranitidine in human plasma.

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Rapid analysis of ranitidine in biological fluids and determination of its erythrocyte partitioning

Cited by 21 publications

References 11 publications

Pharmacokinetics of Ranitidine in Critically Ill Infants

Pharmacokinetics of Ranitidine in Critically Ill Infants

A novel liquid chromatography/tandem mass spectrometry based depletion method for measuring red blood cell partitioning of pharmaceutical compounds in drug discovery

Determination of Ranitidine in Human Plasma by SPE and ESI-LC-MS/MS for Use in Bioequivalence Studies

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