Determination of ruxolitinib in human plasma by an lcmsms method ujjana nandihalli 1, thomas tarnowski 2, stephanie cape, drew dorshorst 1 and aaron ledvina 1 covance laboratories inc. You may get infections more easily, even serious or fatal infections. A novel, simple, specific, sensitive and reproducible high. Unlike column chromatography, here high pressure is employed in the process. Dosedependent pharmacokinetics of tofacitinib in rats. Liquid chromatographictandem mass spectrometric assay bioline. Tofacitinib is a drug of the janus kinase jak inhibitor class. It is currently approved for the treatment of rheumatoid arthritis ra in the united states and other countries.
Hplc method for the quantitation of tofacitinib in rat plasma and its. Tofacitnib an inhibitor of janus kinase jakwhich is available orally with anti inflammatory and also with immunomodulatory. This study investigated the pharmacokinetics of tofacitinib in rats and the effects of firstpass metabolism on tofacitinib pharmacokinetics. Stability indicating hplc method for the quantification of. The chromatographic method was carried out using isocratic elution programme on c 18. It was found that tofacitinib was stable under photolytic condition, but degraded obviously in acidic, basic, thermal and oxidative conditions. Chromatographic analysis was performed on phenomenex luna c18 ods column having 250 mm. Jul 05, 2019 tofacitinib 10 mgkg was infused for 1 min via the jugular vein n 3. At the end of each chapter there is a list of references andor further reading which will help the reader to develop their expertise in the technique. In phase 3 p3 studies, tofacitinib demonstrated safety and efficacy at 5 and 10 mg bid when used as monotherapy or with conventional synthetic cs dmards csdmards. The present invention is related to a simple and efficient process for the preparation of tofacitinib citrate 1, a pfizer molecule approved for the treatment of rheumatoid arthritis. Call your doctor if you have a fever, chills, aches, tiredness, cough, trouble breathing, skin sores, diarrhea, weight loss, or burning when you urinate. Handbook of pharmaceutical analysis by hplc, volume 6 1st. High throughput screening and bioanalysis development.
At the end of each chapter there is a list of references andor further reading which will help the reader to. The aqueous ph solubility of tofacitinib the citrate salt was determined to be 0. The aim is to develop simple validated analytical method for analysis of tofacitinib by uv spectroscopy and to study the forced degradation and stress conditions have been used to detect the stability of tofacitinib. Dissolution, content uniformity, assay, drug impurities and stability, in process and cleaning verification. Tofacitinib is a potent inhibitor of janus kinase 3 jak3 with some jak1 inhibitory activity as well. The objective of the present work is to develop simple, precise and reliable hplc method for the analysis of tofacitinib in bulk and laboratory prepared physic al admixture of tofacitinib. This page looks at how it is carried out and shows how it uses the same principles as in thin layer chromatography and column chromatography.
The invention discloses a determination method for the content of tofacitinib citrate and related substances of the tofacitinib citrate by reversed phase high performance liquid chromatography. Nov 17, 2014 the process relies upon an improved process for the preparation of a key intermediate 3r,4r1benzyl4methylpiperidin3ylmethylamine as tartarate salt 3 and its simple and impurityfree conversion to tofacitinib citrate 1. But also due to its efficiency in the analysis of compounds, it is regarded as high performance liquid chromatography. Purchase handbook of pharmaceutical analysis by hplc, volume 6 1st edition. The limit of detection and quantification were found. High performance liquid chromatography is a powerful tool in analysis. The chromatographic analysis was performed on a waters alliance system using a gradient mobile phase conditions at a flow rate of 1. The separation was achieved on a lichrospher c18 column 250 mm.
Includes dosages for rheumatoid arthritis, psoriatic arthritis and ulcerative colitis. The volume of each bile sample was measured, and an aliquot of each was stored at. Development of a validated reverse phase liquid chromatographic assaymethod for determination of tofacitinib in pure form and in physical. Determination of ruxolitinib in human plasma by an lcmsms. An improved and efficient process for the preparation of.
Tofacitinib can be considered a bcs class 3 drug because of high aqueous solubility and moderate permeability. Tofacitinib was estimated by rp hplc using methanol, water mixture as mobile phase. Development and validation of a rphplc method for the. They binds with jak inorder to protect activation of jak signal transducers and the. The process relies upon an improved process for the preparation of a key intermediate 3r,4r1benzyl4methylpiperidin3ylmethylamine as tartarate salt 3 and its simple and impurityfree conversion to tofacitinib citrate 1. Development and validation of an hplcdad method for the. Selection of an appropriate column is an important task for successful development of hplc method. Msms method has been developed and validated for simultaneous quantification of methotrexate mtx and tofacitinib tfb in rat plasma 50.
Materials used api of tofacitinib was procured from varun herbals, hyderabad, india. A simple, rapid, selective, and reproducible reversedphase high performance liquid chromatographic rphplc method has been developed and validated for the estimation of losartan potassium in dissolution samples of losartan potassium immediate and sustained release tablets. Development and validation of a novel rphplc method for. Tofacitinib is a synthetic molecule corresponding to a molecular weight of 312. Tofacitinib, sold under the brand xeljanz among others, is a medication used to treat rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis and ulcerative colitis. Development and validation of a simple and sensitive. Sampath kumar reddy govind, nagaraju ch vs, rajan st, eshwaraiah s, kishore m and chakravarthy ie.
Rjpt development of a validated reverse phase liquid. This is achieved by using the most commonly employed phenomenex rp 18 150 x 4. Use caution when treating patients at higher cardiovascular risk including known coronary. Jan 26, 2015 a novel, simple, specific, sensitive and reproducible high. Tofacitinib 10 mgkg was infused for 1 min via the jugular vein n 3. The process relies upon an improved process for the preparation of a key intermediate 3r,4r1benzyl4methylpiperidin3ylmethylamine as tartarate salt 3 and. Hplc system connected with photo diode array pda detector to obtain the. Hplc grade methanol was purchased from merck india. Detailed tofacitinib dosage information for adults. Development and validation of a normal phase hplc method for separation of anacardic acid isomers in cashew nut shell liquid praveen kumar s. As the impact of nintedanib on the effectiveness of hormonal contraception is unknown, advise women using hormonal contraceptives to add a barrier method. The forced degradation studies results are given below in below table2. Tofacitinib 33r,4r4methyl3methyl7hpyrrolo2,3dpyrimidin4ylaminopiperidin1yl3 oxopropanenitrile is a new class of drug called janus kinase inhibitor. The current invention is aimed at addressing process development issues related to quality and yields.
The bioanalytical procedure involves extraction of tofacitinib and itraconazole internal standard, is from rat plasma with a simple liquidliquid extraction process. Tofacitinibcp690550 lcms supplied by abmole bioscience. The aim is to develop simple validated analytical method for analysis of tofacitinib by rp hplc in pure and laboratory prepared physical admixtures. Tofacitinib was estimated by rp hplc using methanol,water mixture as mobile phase. The method was optimized using buffer prepared by dissolving 2. Request pdf development and validation of a rphplc method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study. Request pdf development and validation of a rp hplc method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study a novel, simple, specific, sensitive. Although the dosedependent pharmacokinetics of tofacitinib have been described in humans 7,8, the mechanisms. Ebscohost serves thousands of libraries with premium essays, articles and other content including stability indicating hplc method for the quantification of tofacitinib citrate and its related substances. Request pdf development and validation of a rphplc method for the quantitation of tofacitinib in rat plasma and its application to a pharmacokinetic study a novel, simple, specific, sensitive. Ms method was developed for separation, identification and characterization of the process. Liquid chromatographictandem mass spectrometric assay for simultaneous quantitation of tofacitinib, cabozantinib.
If youve ever had hepatitis b or c, using tofacitinib can cause this virus to. Hplc analysis is one of the types of chromatography used to isolate and analyze mixtures. Tofacitinib is a novel, oral janus kinase inhibitor. It blocks downstream stat signaling resulting in potent inhibition of inflammatory cytokines with resultant immunosuppressive and antiinflammatory activity. In addition to providing an introduction to hplc for pharmaceutical analysis it is intended that this book will be a useful resource. L using phenacetin as an internal standard is, as per the us food and drug administration guidelines. Water was distilled and purified with the merck millipore system. Pdf stability indicating hplc method for the quantification. Here, we examine the safety profile of tofacitinib 5 mg bid as monotherapy and. Bile samples were collected over various time periods, from 01, 12, 24, 46, and 624 h. The objectives of this study were to summarize the pharmacokinetics and metabolism of tofacitinib in humans, including clearance mechanisms.
A novel stability indicating chromatographic method. A novel stability indicating chromatographic method development. Determination of ruxolitinib in human plasma by an lc. The bioanalytical procedure involves extraction of tofacitinib and itraconazole internal standard, is from rat plasma with a simple liquidliquid. Rjpt stress degradation studies and development of. Analysis was performed on an agilent, zorbax eclipse xdb c 18. Hplc in full form is highpressure liquid chromatography.
Identification of related substances in tofacitinib. Abstract stability indicating hplc method for the quantification of tofacitinib citrate and its related substances authors. Tofacitinibcp690550lcms supplied by abmole bioscience. Development and validation of a normal phase hplc method. Identification of related substances in tofacitinib citrate. Tofacitinib cp690550 citrate high performance liquid chromatography analysis information product name. Tofacitinib is metabolized through hepatic oxidation and ndemethylation, primarily by cytochrome p450 cyp 3a4, but also by cyp2c19 and glucuronide conjugation 3. Development and validation of a normal phase hplc method for. The pharmacokinetics, metabolism, and clearance mechanisms. In summary, we have developed and validated a sensitive, spe cific and reproducible hplc assay to quantitate tofacitinib in rat plasma.
Tofacitinib cp690550,tasocitinib high performance liquid chromatography analysis information product name. High performance liquid chromatography is basically a highly improved form of column. Intravenous administration of 5, 10, 20, and 50 mgkg tofacitinib showed that the dosenormalized area under the plasma concentrationtime curve from time zero to infinity auc was significantly higher at 50 mgkg than at lower doses. The high resolution tofms and msms were used for determination and structural identification of the related substances. A safety analysis of tofacitinib 5mg twice daily administered. Tofacitinib is an oral janus kinase inhibitor for the treatment of rheumatoid arthritis ra. Stability indicating hplc method for the quantification of tofacitinib. Stability indicating hptlc method for determination of tofacitinib citrate authors. Tofacitinib33r,4r4methyl3methyl7hpyrrolo2,3dpyrimidin4ylaminopiperidin1yl3 oxopropanenitrile is a new class of drug called janus kinase inhibitor.
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