Forced degradation study of racecadotril: Effect of co-solvent, characterization of degradation products by UHPLC-Q-TOF-MS/MS, NMR and cytotoxicity assay.

Abstract:

:Racecadotril, an enkephalinase inhibitor, was subjected to hydrolysis (acidic and alkaline), oxidation, photolysis and thermal stress, as per ICH specified conditions. The drug showed extensive degradation under acidic, basic hydrolysis and oxidative stress conditions whereas, it was stable under other stress conditions. A total of seven degradation products (DPs) were observed. The chromatographic separation was optimized on Acquity HSS Cyano (100×2.1mm, 1.8μ) column using 0.1% formic acid and acetonitrile as mobile phase in gradient mode. Six DPs were characterised by LC-MS/MS and DP1 by GC-MS. The major DPs (DP 2 and DP 5) were isolated and characterised by NMR. This is a typical case of degradation where co solvent methanol reacts with racecadotril leading to the formation of pseudo DPs, DP 6 and DP 5. Interestingly the MS/MS spectra of protonated drug, DP 4 and DP 7 showed product ions which were formed due to intramolecular benzyl migrations. In vitro cytotoxic activity studies on isolated DP 2 and DP 5 revealed that the former has no cytotoxic nature, whereas the latter has potential pulmonary and hepatic toxicity.

journal_name

J Pharm Biomed Anal

authors

Chiguru V,Lingesh A,R S,N S

doi

10.1016/j.jpba.2016.05.008

subject

Has Abstract

pub_date

2016-09-05 00:00:00

pages

9-17

eissn

0731-7085

issn

1873-264X

pii

S0731-7085(16)30245-X

journal_volume

128

pub_type

杂志文章
  • Simultaneous determination of phytoestrogens and key metabolites in breast cancer patients' urine by liquid chromatography-tandem mass spectrometry.

    abstract::A novel, selective and sensitive liquid chromatography-tandem mass spectrometry method has been developed and validated for the simultaneous determination of phytoestrogens and their key metabolites in human urine in this study. This method includes internal standard (IS) screening, analytical sample preparation proce...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2009.06.032

    authors: Yu J,Wu Q,Qiao S,Yu Z,Jin N,Yu B

    更新日期:2009-12-05 00:00:00

  • Simultaneous determination of sesquiterpenes and pyrrolizidine alkaloids from the rhizomes of Petasites hybridus (L.) G.M. et Sch. and dietary supplements using UPLC-UV and HPLC-TOF-MS methods.

    abstract::UPLC-UV and HPLC-TOF-MS methods have been developed for the analysis of major sesquiterpenes and pyrrolizidine alkaloids from rhizomes of Petasites hybridus (L.) G.M. et Sch. (Family, Asteracea) and dietary supplements claiming to contain P. hybridus. The best results were obtained with Acquity UPLC™ HSS T3 (100 mm × ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.05.021

    authors: Avula B,Wang YH,Wang M,Smillie TJ,Khan IA

    更新日期:2012-11-01 00:00:00

  • Characterization of eptifibatide during drug formulation stability assays.

    abstract::The objective of the study was to determine the identity of a new impurity detected in HPLC chromatograms of research samples of eptifibatide manufactured by a new process and formulated into drug product. The identification of the unknown impurity was required in order to understand the mechanism of its formation. Th...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(03)00409-6

    authors: Wang R,Feder D,Hsieh F

    更新日期:2003-12-04 00:00:00

  • Exploration and classification of chromatographic fingerprints as additional tool for identification and quality control of several Artemisia species.

    abstract::The World Health Organization accepts chromatographic fingerprints as a tool for identification and quality control of herbal medicines. This is the first study in which the distinction, identification and quality control of four different Artemisia species, i.e. Artemisia vulgaris, A. absinthium, A. annua and A. capi...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2014.02.006

    authors: Alaerts G,Pieters S,Logie H,Van Erps J,Merino-Arévalo M,Dejaegher B,Smeyers-Verbeke J,Vander Heyden Y

    更新日期:2014-07-01 00:00:00

  • Comparative studies on glycoproteins expressing polylactosamine-type N-glycans in cancer cells.

    abstract::In the series of our previous reports, we showed that some cancer cell lines specifically express polylactosamine-type N-glycans and such glycans were often modified with fucose and sulfate residues. To confirm the proteins expressing these glycans, glycopeptide mixture obtained by digestion of whole protein fractions...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.06.035

    authors: Mitsui Y,Yamada K,Hara S,Kinoshita M,Hayakawa T,Kakehi K

    更新日期:2012-11-01 00:00:00

  • Simultaneous qualitative and quantitative analysis of triterpenic acids, saponins and flavonoids in the leaves of two Ziziphus species by HPLC-PDA-MS/ELSD.

    abstract::The leaves of Ziziphus jujuba and Z. jujuba var. spinosa have been utilized as crude drugs for their health benefits in China for thousands of years. To control their quality, a reliable method based on high-performance liquid chromatography coupled with photo diode array and electrospray ionization tandem mass spectr...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2011.05.025

    authors: Guo S,Duan JA,Tang Y,Qian Y,Zhao J,Qian D,Su S,Shang E

    更新日期:2011-09-10 00:00:00

  • Comparison of drug substance impurity profiles generated with extended length columns during packed-column SFC.

    abstract::The current study assesses the effect of extending column length during gradient packed column sub/supercritical fluid chromatography (PCSFC) experiments on the detection of known and unknown impurities in a drug substance sample. Quantitative drug substance impurity profiles were generated and compared using multiple...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(01)00405-8

    authors: Roston DA,Ahmed S,Williams D,Catalano T

    更新日期:2001-10-01 00:00:00

  • HPTLC determination of nimesulide from pharmaceutical dosage forms.

    abstract::A simple, rapid, reproducible and stability indicating high performance thin-layer chromatographic method for the analysis of Nimesulide both the bulk drug and from pharmaceutical formulations is reported. The mobile phase selected consists of Cyclohexane-Ethylacetate [60:40, v/v]. It gave compact spots both for Nimes...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(00)00597-5

    authors: Patravale VB,D'Souza S,Narkar Y

    更新日期:2001-06-01 00:00:00

  • Racemization of 6-methoxydihydrosanguinarine in methanol investigated by enantioselective dynamic HPLC.

    abstract::A biologically active benzophenanthridine alkaloid, 6-methoxydihydrosanguinarine (MS), was isolated from Hylomecon plants. Although enantiomers of MS can be separated by chiral HPLC, its isomers rapidly form a racemic mixture in methanol. The rate constants for the racemization of MS enantiomers were 9.20x10(-4)s(-1) ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2009.08.014

    authors: Wu E,Jung SH,Chen J,Kim YH,Park KL,Lee W,Kang JS

    更新日期:2010-01-05 00:00:00

  • Simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in rat plasma by liquid chromatography-tandem mass spectrometry and application in pharmacokinetic studies after oral administration of traditional Chinese

    abstract::A sensitive, rapid and selective liquid chromatography-tandem mass spectrometry (LC-MS-MS) method was developed and validated for the simultaneous determination of baicalin, baicalein, wogonin, berberine, palmatine and jatrorrhizine in scutellaria-coptis herb couple in rat plasma. After protein precipitation with acet...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2010.04.002

    authors: Feng J,Xu W,Tao X,Wei H,Cai F,Jiang B,Chen W

    更新日期:2010-11-02 00:00:00

  • Restoration of hepatocytes function following decompression therapy in extrahepatic biliary obstructed patients: metabolite profiling of bile by NMR.

    abstract::Prolonged biliary obstruction and infection cause retention of biliary constituents in liver followed by hepatocyte dysfunction. Decompression therapy is important for both management and prognostic reasons and restores hepatocyte function. Quantitative metabolite profiling of bile using NMR spectroscopy at the time o...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2011.04.010

    authors: Bala L,Tripathi P,Choudhuri G,Khetrapal CL

    更新日期:2011-08-25 00:00:00

  • High-throughput miniaturized immunoassay for human interleukin-13 secreted from NK3.3 cells using homogenous time-resolved fluorescence.

    abstract::A miniaturized immunoassay for human interleukin-13 (IL-13) using homogeneous time-resolved fluorescence (HTRF) has been developed. In this assay, IL-13 which was secreted from NK3.3 cells stimulated with interleukin-2 (IL-2) was detected by measuring the time-resolved fluorescence after adding a mixture of three reag...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(01)00596-9

    authors: Enomoto K,Araki A,Nakajima T,Ohta H,Dohi K,Préaudat M,Seguin P,Mathis G,Suzuki R,Kominami G,Takemoto H

    更新日期:2002-04-01 00:00:00

  • Knowledge-based metabolite annotation tool: CEU Mass Mediator.

    abstract::CEU Mass Mediator (CMM) is an on-line tool for aiding researchers when performing metabolite annotation. Its database is comprised of 279,318 real compounds integrated from several metabolomic databases including Human Metabolome Database (HMDB), KEGG and LipidMaps and 672,042 simulated compounds from MINE. In additio...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2018.02.046

    authors: Gil de la Fuente A,Godzien J,Fernández López M,Rupérez FJ,Barbas C,Otero A

    更新日期:2018-05-30 00:00:00

  • Capillary electrophoresis in analysis of veterinary drugs.

    abstract::Antibiotics are extensively applied in veterinary medicine for the treatment of various bacterial infections. Because of their use in food producing animals, the risk of occurrence of unwanted residues in edible products exists. To ensure human food safety, The European Union has defined maximum residue limits (MRLs) ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(03)00195-x

    authors: Kowalski P,Oledzka I,Lamparczyk H

    更新日期:2003-08-08 00:00:00

  • RP-HPLC and NMR study of cis-trans isomerization of enalaprilat.

    abstract::The angiotensin converting enzyme inhibitor, enalaprilat can exist in solution as cis and trans conformers which interconvert around the amide bond at room temperature. A HPLC with UV detection was performed to study the influence of various chromatographic operational conditions on both rotamers separation and elutio...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(02)00661-1

    authors: Bouabdallah S,Trabelsi H,Ben Dhia T,Sabbah S,Bouzouita K,Khaddar R

    更新日期:2003-03-26 00:00:00

  • The efficient use of microcolumns in chromatographic systems.

    abstract::Microcolumn techniques involving pre-column concentration and post-column derivatization make good use of micro-scale high-performance liquid chromatography. The efficient use of microcolumns is illustrated by some applications to the analysis of amino acids, bile acids and catecholamines. The potential of new detecto...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/0731-7085(84)80073-4

    authors: Ishii D,Goto M,Takeuchi T

    更新日期:1984-01-01 00:00:00

  • Determination of GHB and its precursors (GBL and 1,4-BD) in dietary supplements through the synthesis of their isotopologues and analysis by GC-MS method.

    abstract::Gamma-hydroxybutyric acid (GHB) and its "pro-drugs", gamma-butyrolactone (GBL) and 1,4 butanediol (1,4-BD), are drugs of abuse with depressant effects on the central nervous system. Many analytical methods have been proposed for the quantitative determination of these compounds mainly in biological matrices but only f...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2012.10.006

    authors: Rosi L,Frediani P,Bartolucci G

    更新日期:2013-02-23 00:00:00

  • Supercritical fluid chromatography-tandem mass spectrometry for high throughput bioanalysis of small molecules in drug discovery.

    abstract::Liquid chromatography tandem mass spectrometry (LC-MS/MS) has been a golden standard for high throughput small molecule bioanalysis in drug discovery for decades. Supercritical fluid chromatography (SFC) has caught more attention in recent decade due to its advantages of greener mobile phase, lower backpressure and hi...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2018.10.021

    authors: Zhang X,Ding X,Wang J,Dean B

    更新日期:2019-02-05 00:00:00

  • Application of derivative-differential UV spectrophotometry and ratio derivative spectrophotometric determination of mephenoxalone and acetaminophen in combined tablet preparation.

    abstract::A method is presented for the direct determination of mephenoxalone and acetaminophen in combined pharmaceutical dosage forms without prior separation. The first method, derivative-differential spectrophotometry, comprised of measurement of the difference absorptivities derivatized in the first order (deltaD1) of a ta...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(99)00157-0

    authors: Erk N

    更新日期:1999-11-01 00:00:00

  • Quality control of pharmaceutical formulations containing cisplatin, carboplatin, and oxaliplatin by micellar and microemulsion electrokinetic chromatography (MEKC, MEEKC).

    abstract::A micellar electrokinetic chromatography (MEKC) method was developed for the determination of cisplatin, carboplatin, and oxaliplatin in pharmaceutical formulations. The background electrolyte consisted of a phosphate buffer (pH 7.0; 25 mM) with sodium dodecyl sulfate (80 mM). The applied voltage was 30 kV and the sam...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2011.01.029

    authors: Nussbaumer S,Fleury-Souverain S,Schappler J,Rudaz S,Veuthey JL,Bonnabry P

    更新日期:2011-05-15 00:00:00

  • Quantification of atorvastatin calcium in tablets by FT-Raman spectroscopy.

    abstract::The FT-Raman quantification of atorvastatin calcium in tablets was performed using the partial least squares (PLS), principal component regression (PCR) and counter-propagation artificial neural networks (CP-ANN) methods. To compare the predictive abilities of the elaborated models, the relative standard errors of pre...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2008.10.015

    authors: Mazurek S,Szostak R

    更新日期:2009-01-15 00:00:00

  • Polarographic determination of benzaldehyde in benzyl alcohol and sodium diclofenac injection formulations.

    abstract::A rapid and sensitive polarographic method was developed for qualitative as well as quantitative analysis of the neurotoxic contaminant benzaldehyde in Na-diclofenac injections and in benzyl alcohol used for parental formulations. A well-defined differential pulse (DP) polarographic peak or a sampled direct current (S...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(02)00340-0

    authors: Kazemifard AG,Moore DE,Mohammadi A

    更新日期:2002-09-05 00:00:00

  • Development and optimization of a reversed-phase high-performance liquid chromatographic method for the determination of piperacillin and tazobactam in tazocin injectable powder.

    abstract::A reversed phase high-performance liquid chromatographic method with detection at 220 nm was developed and validated for the determination of piperacillin, I, and tazobactam, II, in Tazocin injectable powder. Acetaminophen was used as internal standard. A Hypersil BDS RP-C(18) column (250 x 4.6 mm), 5 microm particle ...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(02)00129-2

    authors: Marselos SC,Archontaki HA

    更新日期:2002-07-31 00:00:00

  • Solid-phase extraction of galloyl- and caffeoylquinic acids from natural sources (Galphimia glauca and Arnicae flos) using pure zirconium silicate and bismuth citrate powders as sorbents inside micro spin columns.

    abstract::Galloyl- and caffeoylquinic acids are among the most important pharmacological active groups of natural compounds. This study describes a pre-step in isolation of some selected representatives of these groups from biological samples. A selective solid-phase extraction (SPE) method for these compounds may help assign c...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2013.05.029

    authors: Hussain S,Schönbichler SA,Güzel Y,Sonderegger H,Abel G,Rainer M,Huck CW,Bonn GK

    更新日期:2013-10-01 00:00:00

  • Bioactive phenols in algae: the application of pressurized-liquid and solid-phase extraction techniques.

    abstract::A new extraction technique based on the off-line combination of pressurized-liquid with solid-phase extraction (PLE-SPE) is described. The method was used for the extraction of bioactive phenolic acids (protocatechuic, p-hydroxybenzoic, 2,3-dihydroxybenzoic, chlorogenic, vanillic, caffeic, p-coumaric, salicylic acid),...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2009.03.027

    authors: Onofrejová L,Vasícková J,Klejdus B,Stratil P,Misurcová L,Krácmar S,Kopecký J,Vacek J

    更新日期:2010-01-20 00:00:00

  • Determination of the kinetics of rat UDP-glucuronosyltransferases (UGTs) in liver and intestine using HPLC.

    abstract::Uridinediphosphoglucuronosyl transferases (UGTs) are a group of membrane bound proteins which catalyze the transfer of glucuronic acid from UDP-glucuronic acid to a wide variety of xenobiotics and drug molecules enabling them to be eliminated. The major UGT isoforms found in the rat are 1A1, 1A6, 2B1 and 2B12. Convent...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/s0731-7085(00)00241-7

    authors: Narayanan R,LeDuc B,Williams DA

    更新日期:2000-04-01 00:00:00

  • Clara cell secretory protein: determination of serum levels by an enzyme immunoassay and its importance as an indicator of bronchial asthma in children.

    abstract::Clara cell secretory protein (CC16) is a 16kDa protein secreted by Clara cells in the lining fluid of bronchiolar and bronchial epithelium. CC16 presents several biologic properties, and has been shown to have immunomodulatory and anti-inflammatory activity. It may play a role in controlling inflammation in the airway...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/S0731-7085(03)00570-3

    authors: Gioldassi XM,Papadimitriou H,Mikraki V,Karamanos NK

    更新日期:2004-03-01 00:00:00

  • Simultaneous determination of lamotrigine, phenobarbitone, carbamazepine and phenytoin in human serum by high-performance liquid chromatography.

    abstract::A simple reversed-phase high-performance liquid chromatography (HPLC) method was developed for the simultaneous estimation of the antiepileptic drugs (AEDs) lamotrigine (LTG), phenobarbitone (PB), carbamazepine (CBZ) and phenytoin (PHT) in human serum. The procedure involves extraction of the AEDs by mixing 200 microl...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2005.02.045

    authors: Patil KM,Bodhankar SL

    更新日期:2005-09-01 00:00:00

  • Phytochemical analysis and anti-inflammatory evaluation of compounds from an aqueous extract of Croton cajucara Benth.

    abstract::Croton cajucara Benth. is a medicinal plant popularly used in the Brazilian Amazonia, where it is known as sacaca, being consumed as tea, decoction or infusion of the leaves and stem bark. From a decoction of the leaves, a comprehensive phytochemical analysis was developed by liquid chromatography-mass spectrometry. M...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2017.07.032

    authors: Nascimento AM,Maria-Ferreira D,Dal Lin FT,Kimura A,de Santana-Filho AP,Werner MFP,Iacomini M,Sassaki GL,Cipriani TR,de Souza LM

    更新日期:2017-10-25 00:00:00

  • Chemical markers for quality control of bran-fried sulfur-fumigated Paeoniae Radix Alba.

    abstract::In traditional Chinese medicine practice, crude herbs are often subjected to traditional processing (Paozhi in Chinese) for a special medicinal purpose. Bran-frying is one of processing methods for Paeoniae Radix Alba (PRA). Previous studies found that paeoniflorin and paeoniflorin sulfonate, a principle bioactive com...

    journal_title:Journal of pharmaceutical and biomedical analysis

    pub_type: 杂志文章

    doi:10.1016/j.jpba.2018.07.003

    authors: Xu YY,Long F,Zhang YQ,Xu JD,Kong M,Li SL

    更新日期:2018-09-10 00:00:00