Reliable method for the determination of ranitidine by liquid chromatography using a microvolume of plasma (original) (raw)
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Journal of Chromatography B: Biomedical Sciences and Applications, 2001
A simple high-performance liquid chromatographic procedure was developed for the determination of ranitidine in human plasma. The method entailed direct injection of the plasma samples after deproteination using perchloric acid. The chromatographic separation was accomplished with an isocratic elution using mobile phase consisting of 21 mM disodium hydrogen phosphate-triethylamine-acetonitrile (1000:60:150, v / v), pH 3.5. Analyses were run at a flow-rate of 1.3 ml / min using a mbondapak C column and ultraviolet detection at a wavelength of 320 nm. The method was specific and sensitive, 18 with a quantification limit of approximately 20 ng / ml and a detection limit of 5 ng / ml at a signal-to-noise ratio of 3:1. The mean absolute recovery was about 96%, while the within-and between-day coefficient of variation and percent error values of the assay method were all less than 8%. The linearity was assessed in the range of 20-1000 ng / ml plasma, with a correlation coefficient of greater than 0.999. This method has been used to analyze several hundred human plasma samples for bioavailability studies.
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 l). 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 TM 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 ionisa-tion (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.
High Performance Liquid Chromatographic Determination of Ranitidine in Human Plasma
J Liq Chromatogr Relat Techno, 1995
a Chloroform extraction; average of data obtained using both chromatographic systems. formation of high molecular weight materials, and an HPLC method is currently being developed for the analysis of these products. The surprising disparity between the USP and HPLC assay results can be rationalized when the data in Table IV are considered. Although both methods rely on UV absorption, the USP technique cannot quantify the dimer and merely includes it with the anthralin level. However, a discrepancy between the results is still evident after correcting the USP data for the presence of dimer. The majority of these ointments contained-70% (range 44-92%) of the theoretical amount of anthralin, the remaining 30% being various quantities of the dimer, quinone, and, perhaps, high molecular weight mate r i a 1 s. The need to check anthralin and its preparations must be emphasized, and the danger of further decomposition of samples in use cannot be ignored. REFERENCES (1) B.
ORIENTAL JOURNAL OF CHEMISTRY , 2020
Ranitidine is a histamine-2 receptor blocker and it is effective against peptic ulcer, gastroesophageal reflux disease and heart burn. The main objective of this study was to develop and validate an easy, affordable and cost-effective method for the determination of ranitidine in tablet dosage form. The development and validation study was performed under the guidance of ICH and USP. Results showed that the proposed validated method has good accuracy with % RSD of 0.60. Repeatability and intermediate precision suggested good precision whereas the value of correlation coefficient 0.9999 confirmed about the linearity of the method. The system suitability data and similarity factors were also found within the permissible range. The specificity study revealed that there was no placebo and diluent effect on the absorbance. Further, stability study of analytical solutions as well as estimation of drug content from market products were also performed.
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 338 nm (ex)/523 nm (em). Plasma samples were extracted with diethyl ether alkalinized with 1 M sodium hydroxide. Ephedrine HCl (EPH-HCl) was used as internal standard. Both, RAN and EPH were completely derivatized after heating at 60 • C for 10 min in sodium bicarbonate solution (pH 9.5). The derivatized samples were analyzed by HPLC using Agilent Zorbax Extended C 18 column (150 mm × 4.6 mm i.d.) and mobile phase consists of 48% acetonitrile and 52% sodium acetate solution (0.02 M, pH 4.6). The linearity of the method was in the range of 0.025-10 g/ml. The limits of detection (LOD) and quantification (LOQ) were 7.5 ± 0.18 and 22.5 ± 0.12 ng/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 5 mg/kg ranitidine HCl.
Journal of Chromatography B, 2002
A sensitive and simple HPTLC method was developed for estimation of ranitidine in human urine. The drug was extracted from urine after basification using dichloromethane. Dichloromethane extract was spotted on silica gel 60 F TLC plate 254 and was developed in a mixture of ethyl acetate-methanol-ammonia (35:10:5 v / v) as the mobile phase and scanned at 320 nm. The R value obtained for the drug was 0.6760.03. The method was validated in terms of linearity (50-400 ng / spot), F precision and accuracy. The average recovery of ranitidine from urine was 89.35%. The proposed method was applied to evaluate bioequivalence of two marketed ranitidine tablet formulations (150 mg, Formulation 1 and Formulation 2) using a crossover design by comparing urinary excretion data for unchanged ranitidine in six healthy volunteers. Various pharmacokinetic parameters like peak excretion rate [(dAU / dt) ], time for peak excretion rate (t), AUC , AUC , max max 0-24 0-c umulative amount excreted were calculated for both formulations and subjected to statistical analysis. The relative bioavailability of Formulation 2 with respect to Formulation 1 was 93.76 and 95.31% on the basis of AUC and 0-24 cumulative amount excreted, respectively. Statistical comparison of various pharmacokinetic parameters indicated that the two ranitidine tablet formulations are bioequivalent.
A rapid, simple and sensitive spectrophotometric method has been developed for the determination of ranitidine hydrochloride in pharmaceutical pure and dosage forms. The method depends on the charge-transfer complex formation between ranitidine bases as n-electron donor with chloranil as-acceptor to give a colored complex that absorbs maximally at 550 nm. Beerís law is obeyed in the concentration ranges 2-40µg/mL with molar absorptivity of 2.510 4 L mole-1 cm-1. The proposed method is precise, accurate and specific for the quantitative determination of drug in bulk and dosage forms. The results of analysis of commercial formulations and the recovery study (standard addition method) of ranitidine suggested that there is no interference from any excipients, which are present in pharmaceutical formulations of ranitidine. Statistical comparison of the results was performed with regard to accuracy and precision using studentís ttest and F-ratio at 95% confidence level. There is no significant difference between the reported and proposed methods with regard to accuracy and precision.
Comparative Bioavailability of Ranitidine Tablets in Healthy Volunteers
Iranian Journal of Pharmaceutical Research, 2010
The pharmacokinetic parameters of domestic and imported ranitidine hydrochloride tablets (Ranitidine, formulated and manufactured by Kharazmi Pharmaceuticals, Iran, and Zantac manufactured by Glaxo, UK) were measured in 14 healthy subjects following oral administration of a single 300-mg dose of each brand and compared for bioequival ence evaluation. The pharmaceutical equivalency of both formulations was shown by in vitro characterization and dissolution testing. The comparative bioavailability of the two products was then determined in a single-blind, single dose, randomized, cross-over study in 14 healthy volunteers. A sensitive, rapid and precise high performance liquid chromatography (HPLC) method was used to measure concentrations of ranitidine in plasma samples collected up to 12 hours following each dose. Pharmacokinetic param eters, including C max, Tmax, AUC0-t, AUC0-∞, elimination rate constant (k) and hal f life were determined for both formulations. Analysis of the da...
Revista Brasileira de Ciência do Solo, 2002
The aim of this study was to describe the double peak plasma pharmacokinetic profile of ranitidine after oral administration to healthy volunteers using non-compartmental and compartmental analysis. A single 300 mg dose of ranitidine was given to ten healthy volunteers (5 male and 5 female). Blood samples were drawn at different times and analyzed by HPLC. Plasma profiles were evaluated by non-compartmental and compartmental approaches. The non-compartmental parameters determined were k (0.0054 ± 0.0010 min-1), t 1/2 (2.2 ± 0.4 h), Vd ss /F (265.3 ± 70.6 L), Cl/F (84.8 ± 24.3 L/h) and AUC (225916 ± 54099 ng*min/mL). The compartmental analysis was carried out using a two compartments body model, with first order absorption from two different sites. The parameters determined were k 21 (0.0149 ± 0.0133 min-1), k a1 (0.0117 ± 0.0073 min-1), k a2 (0.1496 ± 0.1699 min-1), Vc (128 ± 75.2 L), a (0.0299 ± 0.0319 min-1), b (0.0074 ± 0.0014 min-1) and time for the beginning of the absorption from the second site (126.7 ± 58.1 min). The model used in the compartmental analysis was adequate to describe the double peak of ranitidine plasma profile and to determine the pharmacokinetic parameters.
2011
In order to evaluate biosimilarity between an innovator and biosimilar product, the FDA recommended a stepwise, riskbased totality of evidence approach. In addition to extensive structural and functional characterization, effort must also be made on preclinical development in terms of animal toxicity studies and the assessment of pharmacokinetics (PK) and immunogenicity. Although there are FDA, EMA guidelines, and whitepapers describing best practices for bioanalytical method development and validation [4-9], there is no clear guidance or recommendation to design and validate bioanalytical assays for biosimilars. The following sections described the experience and lessons we have learned during the course of biosimilar bioanalytical method development and validation. Choosing the right platform In the past four years we have conducted many biosimilar IND enabling drug safety studies with pharmacokinetics and immunogenicity as the critical components, including Rituxan (rituximab, MabThera), Herceptin (trastuzumab), Enbrel (etanercept), Neulasta (pegfilgrastim), Humira (adalimumab) and NESP (darbepoetin alfa). Because these originator drugs were approved some time ago, with the advancement of bioanalytical technologies the PK or immunogenicity methods for biosimilars are not necessarily identical to the ones which were used for the original approval. Ligand binding assays (LBAs) are used to measure the therapeutic level of biologics in biological samples. Many considerations are taken for platform selection. The most commonly used LBA method is ELISA. Compared to electrochemiluminescence (ECL) measurement on Meso Scale Discovery (MSD) and the automated nanoscale immunoassay platform Gyrolab, ELISA's sensitivity and dynamic range are inferior. However, the low cost of an ELISA plate and associated reagent supplies, along with widely used colorimetric plate readers, have rendered a long life for its application. For biologics that require high-doses for efficacy, assay's sensitivity Abbreviations