Aciphex
Direct injection, column switching-liquid chromatographic technique for the estimation of rabeprazole in bioequivalence study.

Singh SS, Jain M, Shah H, Gupta S, Thakker P, Shah R, Lohray BB.

Zydus Research Centre, Sarkhej-Bavla N.H. No. 8A, Moraiya, Ahmedabad 382213, India. sonusingh zyduscadila.com

A rapid, simple and sensitive high-performance liquid chromatography-ultra violet (HPLC-UV) method with column switching between sample pre-treatment column and analytical column was developed for the quantitation of rabeprazole in human plasma; on a Bio-Sample Analysis system (Co-sense for BA) from Shimadzu Corporation, Kyoto, Japan. Zaleplon was used as an internal standard. The method was validated as per USFDA guidelines for the concentration range of 20.0-1200.0 ng/mL and the correlation coefficient were found to be better than 0.999. Recovery of rabeprazole as well as the internal standard from human plasma was more than 90.0%. Rabeprazole was stable in human plasma for 4 months at -70 +/- 5 degrees C and for 20.0 h at ambient temperature. In the auto sampler, the drug was stable for 24.0 h at 4 degrees C. The method was specific as there were no interfering peaks in the human plasma eluting at the retention times of the rabeprazole and the internal standard. The frozen plasma samples containing rabeprazole were stable to three freeze thaw cycles. The bioanalytical method was rugged in terms of inter- and intra-day accuracy and precision. The method was simple, specific, sensitive, precise, accurate and suitable for bioequivalence and pharmacokinetic studies. It was successfully applied to the pilot bioequivalence study of 20mg rabeprazole tablet of German Remedies Ltd. (A division of Cadila Healthcare Ltd.), India versus Pariet tablet of Eisai Ltd. & Janssen-Cilag Ltd., Japan in male human subjects.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15556540&dopt=Abstract rabeprazole Aciphex



Aciphex
Effect of rabeprazole on histamine synthesis in enterochromaffin-like cells of mast cell-deficient (Ws/Ws) rats.

Nakamura S, Watanabe H, Yokota T, Matsui H, Onji M, Maeyama K.

Third Department of Internal Medicine, Ehime University, School of Medicine, Shigenobu-cho, Onsen-gun, Ehime, Japan.

The effect of rabeprazole, the latest proton pump inhibitor, on the serum gastrin concentration, histidine decarboxylase activity and histamine content of the oxyntic mucosa in Wistar rats, mast cell-deficient (Ws/Ws) rats, and their normal type, +/+, rats was investigated. In Wistar rats, 2 weeks of treatment with rabeprazole (30 mg/kg/day, s.c.) induced a 1.8-fold increase in serum gastrin concentration and a 3.9-fold increase in histidine decarboxylase activity of the oxyntic mucosa over the control levels, whereas neither 2- nor 4-week treatment affected the histamine content of the oxyntic mucosa. In Ws/Ws and +/+ rats, the serum gastrin concentration, histidine decarboxylase activity and even histamine content of the oxyntic mucosa were increased significantly as compared with control levels after the 4-week treatment with rabeprazole. Immunohistochemistry using a histamine antibody confirmed the increase in the histamine content of the oxyntic mucosa after the 4-week treatment with rabeprazole. The finding that there were no differences in serum gastrin concentration and histidine decarboxylase activity between Ws/Ws and +/+ rats, both with and without the 4-week treatment, indicates that mast cells do not respond to endogenous hypergastrinemia elicited by acid-inhibitory treatment. Moreover, the present study clarified for the first time that enterochromaffin-like (ECL) cells in Ws/Ws rats synthesize and store histamine in response to gastrin.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=10771028&dopt=Abstract rabeprazole Aciphex



Aciphex
High-performance liquid chromatography method for the quantification of rabeprazole in human plasma using solid-phase extraction.

Ramakrishna NV, Vishwottam KN, Wishu S, Koteshwara M, Kumar SS.

Biopharmaceutical Research, Suven Life Sciences Ltd., Serene Chambers, Road #7, Banjara Hills, Hyderabad 500034, India. nvsrk suven.com

A simple, sensitive and selective HPLC method with UV detection (284 nm) was developed and validated for quantitation of rabeprazole in human plasma, the newest addition to the group of proton-pump inhibitors. Following solid-phase extraction using Waters Oasistrade mark SPE cartridges, the analyte and internal standard (Pantoprazole) were separated using an isocratic mobile phase of 5 mM ammonium acetate buffer (pH adjusted to 7.4 with sodium hydroxide solution)/acetonitrile/methanol (45/20/35, v/v) on reverse phase Waters symmetry C(18) column. The lower limit of quantitation was 20 ng/mL, with a relative standard deviation of less than 8%. A linear range of 20-1000 ng/mL was established. This HPLC method was validated with between- and within-batch precision of 2.4-7.2% and 2.2-7.3%, respectively. The between- and within-batch bias was -1.7 to 2.6% and -2.6 to 2.1%, respectively. Frequently coadministered drugs did not interfere with the described methodology. Stability of rabeprazole in plasma was excellent, with no evidence of degradation during sample processing (autosampler) and 3 months storage in a freezer. This validated method is sensitive, simple and repeatable enough to be used in pharmacokinetic studies.

Online source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15664352&dopt=Abstract rabeprazole Aciphex