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1.
Eur J Pharm Sci ; : 105429, 2020 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-32561460

RESUMO

Poly (vinyl alcohol), PVA, a commonly used excipient to coat tablets, forms insoluble films in the presence of acids and thermal stress. This may lead to drug products failing to meet dissolution specifications over time. Studies were conducted to understand the effect of acid strength, processing conditions, and storage stress on the mechanism of insoluble film formation using PVA and Opadry® II as model systems. Aqueous cast films, prepared by incorporating hydrochloric acid (HCl) into the coating solutions or exposing pre-cast "as is" films to HCl vapors, were used as surrogates to develop analytical methods. To understand effect of acid and processing on coatings, acidified Opadry® II was spray coated onto inert cores under "wet" or "dry" conditions. Samples stored at 50-60 °C were analyzed for film disintegration to understand physical/chemical changes in the polymer. Rate and extent of insoluble films formation was dependent on the acid concentration and thermal stress. Analysis of the films indicated significant de-acetylation and ether bond formation in insoluble aqueous cast films. In contrast, acidified coated films showed only ether bond formation, which increased on stress, forming insoluble films. The reduction in the time to form insoluble films for "wet" versus "dry" coated films was rationalized by considering effect of coating, drying, and storage on the microstructure of acidified PVA and ether bond propagation. The results highlight the need to develop an in-depth understanding of the design space for PVA coated products and storage conditions in presence of acids.

2.
Artigo em Inglês | MEDLINE | ID: mdl-32004940

RESUMO

Flibanserin (FLB) is the first FDA approved drug showed to have significant activity against sexual desire disorder of premenopausal and postmenopausal women. Unfortunately, FLB is used as an adulterant in dietary supplement products as a performance enhancer in sports. Identification of FLB and its metabolites in the biological samples requires an authenticated analytical technique. The aim of this study was to identify N-oxide metabolite of FLB in microsomal and S9 human liver enzyme fractions, rat urine and feces. There are several N-oxide reported as genotoxic impurity or reactive metabolites based on position of N-oxide in piperazine ring. This study also describes the strategy to utilize degradation chemistry for isolation of N-oxide and its step-wise characterization. An LC-MS method has been developed and employed for identifying the N-oxide metabolite of FLB. The targeted N-oxide metabolite in the extracted ion chromatogram of the in vitro and in vivo samples has been confirmed by analyzing the changes in observed mass at m/z 407.1693. Major distinguished abundant ions at m/z 243.1104, 190.0974, 161.0705, 119.0601 confirmed the structure of the metabolite. This study will help to understand the oxidative potential of FLB in toxicokinetic study. The developed method can be useful to identify FLB or its N-oxide metabolite in dope testing in future. This is the first time to report a strategy to utilize degradation chemistry for N-oxide metabolite characterization. In this study, isolated N-oxidative degradation product was used to confirm N-oxide metabolite which was characterized by LC-MS through H/D exchange and structure was ensured by NMR spectroscopy (1H, COSY).


Assuntos
Benzimidazóis , Medição da Troca de Deutério/métodos , Fezes/química , Espectrometria de Massas em Tandem/métodos , Administração Oral , Animais , Benzimidazóis/administração & dosagem , Benzimidazóis/análise , Benzimidazóis/química , Benzimidazóis/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética , Masculino , Oxirredução , Ratos , Ratos Sprague-Dawley
3.
J Pharm Biomed Anal ; 87: 191-217, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-23706957

RESUMO

Liquid chromatography-mass spectrometry (LC-MS) is considered today as a mainstay tool for the structure characterization of minor components like impurities (IMPs) and degradation products (DPs) in drug substances and products. A multi-step systematic strategy for the purpose involves high resolution mass and multi-stage mass studies on both the drug and IMPs/DPs, followed by comparison of their fragmentation profiles. Its successful application requires consideration of many practical aspects at each step. The same are critically discussed in this review.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Preparações Farmacêuticas/análise , Contaminação de Medicamentos , Preparações Farmacêuticas/química , Preparações Farmacêuticas/normas
4.
Anal Chem ; 85(22): 10904-12, 2013 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-24117319

RESUMO

Structural elucidation is an integral part of drug discovery and development. In recent years, due to acceleration of the drug discovery and development process, there is a significant need for highly efficient methodologies for structural elucidation. In this work, we devised and standardized a simple and economical online hydrogen-deuterium exchange methodology, which can be used for structure elucidation purposes. Deuterium oxide (D2O) was infused as a postcolumn addition using the syringe pump at the time of elution of the analyte. The obtained hydrogen/deuterium (H/D) exchange spectrum of the unknown analyte was compared with the nonexchanged spectrum, and the extent of deuterium incorporation was delineated by using an algorithm to deconvolute partial H/D exchange, which confirmed the number of labile hydrogen(s) in the analyte. The procedure was standardized by optimizing flow rates of LC output, D2O infusion, sheath gas, and auxiliary gas using the model compound sulfasalazine. The robustness of the methodology was demonstrated by performing sensitivity analysis of various parameters such as concentrations of analyte, effect of matrices, concentrations of aqueous mobile phase, and types of LC modifiers. The optimized technique was also applied to chemically diverse analytes and tested on various mass spectrometers. Moreover, utility of the technique was demonstrated in the areas of impurity profiling and metabolite identification, taking pravastatin-lactone and N-oxide desloratidine, as examples.


Assuntos
Cromatografia Líquida/métodos , Deutério/química , Hidrogênio/química , Sistemas On-Line , Espectrometria de Massas por Ionização por Electrospray/métodos , Animais , Humanos , Lactonas/química , Loratadina/análogos & derivados , Loratadina/química , Metabolômica , Microssomos Hepáticos/metabolismo , Plasma/metabolismo , Pravastatina/química , Pravastatina/isolamento & purificação , Ratos , Urinálise
5.
Anal Bioanal Chem ; 405(10): 3215-31, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23386001

RESUMO

The present study dealt with the forced degradation behaviour of rosuvastatin under ICH prescribed stress conditions. The drug was found to be labile under acid hydrolytic and photolytic conditions, while it was stable to base/neutral hydrolytic, oxidative and thermal stress. In total, 11 degradation products were formed, which were separated on a C-18 column using a stability-indicating method. LC-MS analyses indicated that five degradation products had the same molecular mass as that of the drug, while the remaining six had 18 Da less than the drug. Structure elucidation of all the degradation products was executed using sophisticated and modern structural characterization tools, viz. LC-MS/TOF, LC-MS(n), on-line H/D exchange and LC-NMR. The degradation pathway and mechanisms of degradation of the drug were delineated. Additionally, in silico toxicity was predicted for all the degradation products using TOPKAT and DEREK software and compared with the drug. This study demonstrates a comprehensive approach of degradation studies during the drug development phase.


Assuntos
Cromatografia Líquida/métodos , Fluorbenzenos/química , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Pirimidinas/química , Sulfonamidas/química , Desenho de Fármacos , Estabilidade de Medicamentos , Fluorbenzenos/toxicidade , Cinética , Estrutura Molecular , Pirimidinas/toxicidade , Rosuvastatina Cálcica , Sulfonamidas/toxicidade
6.
J Pharm Biomed Anal ; 69: 148-73, 2012 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-22521633

RESUMO

With ever increasing regulatory and compendial stringency on the control of impurities (IMPs) and degradation products (DPs) (including genotoxic impurities) in drug substances and finished pharmaceutical formulations, a profound emphasis is being paid on their characterization and analysis at trace levels. Fortunately, there have been parallel tremendous advancements in the instrumental techniques that allow rapid characterization of IMPs and/or DPs at the prescribed levels of ∼0.1%. With this, there is perceptible shift from conventional protocol of isolation and spectral analysis to on-line analysis using modern sophisticated hyphenated tools, like GC-MS, LC-MS, CE-MS, SFC-MS, LC-NMR, CE-NMR, LC-FTIR, etc. These are already being extensively used by industry and also there is tremendous increase in publications in the literature involving their use. This write-up critically reviews the literature for application of hyphenated tools in impurity and degradation product profiling of small molecules. A brief mention is made on possible pitfalls in the experimentation and data interpretation. Appropriate strategies are proposed, following which one can obtain unambiguous characterization of the unidentified IMPs and/or DPs.


Assuntos
Contaminação de Medicamentos , Mutagênicos/química , Preparações Farmacêuticas/análise , Química Farmacêutica/métodos , Cromatografia Gasosa/métodos , Cromatografia Líquida/métodos , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas/métodos , Humanos , Hidrólise , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Preparações Farmacêuticas/química , Reprodutibilidade dos Testes , Espectroscopia de Infravermelho com Transformada de Fourier/métodos , Tecnologia Farmacêutica/métodos
7.
J Pharm Biomed Anal ; 62: 48-60, 2012 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-22300906

RESUMO

Oseltamivir phosphate was subjected to stress degradation conditions prescribed by ICH guideline Q1A (R2). A total of five degradation products (Os I to Os V) were generated under hydrolytic (acid and alkaline) stress conditions. Their unambiguous structural elucidation was carried out using LC-MS, LC-NMR and HR-NMR data. First, accurate masses of Os I, Os II, Os IV and Os V were determined by LC-MS/TOF. Subsequently, (1)H and COSY NMR studies were carried on the drug and these four degradation products using LC-NMR. The structure of Os III was elucidated after preparative isolation and purification, followed by MS/TOF and HR-NMR studies. The degradation products, Os II, Os IV and Os V were characterized as 4-acetamido-5-amino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylic acid, 4,5-diamino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylic acid and ethyl 4,5-diamino-3-(pentan-3-yloxy)cyclohex-1-ene carboxylate, respectively. Os I and Os III were identified as positional isomers of Os II and the drug, respectively, involving N,N-acyl migration from 4-amino to 5-amino position in the ring. Two degradation products (Os IV and Os V) were found to be new and previously unreported. The degradation pathway for all five was outlined and justified mechanistically. In silico toxicity of the drug and degradation products was also assessed using TOPKAT and DEREK software and compared.


Assuntos
Antivirais/química , Oseltamivir/química , Estresse Psicológico , Cromatografia Líquida , Humanos , Espectroscopia de Ressonância Magnética
8.
J Pharm Biomed Anal ; 56(3): 538-45, 2011 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-21757313

RESUMO

Lornoxicam was subjected to forced degradation studies under hydrolytic (acidic, basic and neutral), oxidative, photolytic and thermal stress conditions, as defined under ICH guideline Q1A (R2). The drug degraded significantly in hydrolytic, oxidative and photoneutral conditions, leading to the formation of eight degradation products in total. It was stable on exposure to light and dry heat in the solid state. The stressed samples in which degradation was observed were mixed together and used to develop a stability-indicating HPLC method wherein degradation products were separated from the drug and also from each other. To characterize the degradation products, a complete mass fragmentation pathway of the drug was first established with the help of MS/TOF, MS(n) and H/D exchange mass studies. The same was followed by LC-MS/TOF and on-line H/D exchange experiments on the degradation products. The degradation pathway of the drug was outlined, justified by the mechanisms of formation of the degradation products.


Assuntos
Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Piroxicam/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Estabilidade de Medicamentos , Hidrólise , Oxirredução , Fotólise , Piroxicam/química , Tecnologia Farmacêutica/métodos
9.
Drug Test Anal ; 2(2): 82-90, 2010 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-20878890

RESUMO

The present study demonstrates the applicability of a strategy involving use of liquid chromatography (LC) and liquid chromatography-mass spectrometry (LC-MS) techniques for the identification and characterization of minute quantities of degradation products, without their isolation from the reaction matrix in pure form. Valsartan was used as a model drug. It was subjected to forced degradation studies under the International Conference on Harmonisation (ICH) prescribed conditions of hydrolysis (acid, base and neutral), photolysis, oxidation and thermal stress. The drug showed lability under acid/neutral hydrolytic and photolytic conditions, while it was stable to base hydrolytic, oxidative and thermal stress. Three small degradation products were formed, which were separated on a C-18 column using a gradient method. The same were characterized with the help of their fragmentation pattern and accurate masses obtained upon LC-MS/TOF analyses and online H/D exchange studies. The structures were supported by appropriate mechanistic explanation. The strategy involving use of LC and LC-MS for the identification and characterization of minute quantities of degradation products was applied on a model drug, valsartan. Three degradation products were successfully characterised without their isolation from the reaction matrix in pure form. The structures were supported by appropriate mechanistic explanation.


Assuntos
Química Farmacêutica/métodos , Tetrazóis/química , Tetrazóis/isolamento & purificação , Valina/análogos & derivados , Cromatografia Líquida/métodos , Estabilidade de Medicamentos , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz/métodos , Tetrazóis/metabolismo , Valina/química , Valina/isolamento & purificação , Valina/metabolismo , Valsartana
10.
J Pharm Biomed Anal ; 53(3): 755-61, 2010 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-20554147

RESUMO

Telmisartan, an anti-hypertensive drug, was subjected to stress studies under ICH prescribed conditions of hydrolysis (acidic, neutral and basic), photolysis, oxidation and thermal stress. The drug showed labiality under only photo-acidic condition by forming a single degradation product. HPLC separation of the drug and the degradation product was achieved on C-8 column using gradient method. To characterize the product, a complete mass fragmentation pathway of the drug was initially established. Subsequently, the degradation product peak was subjected to LC-MS/TOF and on-line H/D exchange mass studies. Based on these studies, a tentative structure was assigned to the product as 3-((1,7'-dimethyl-2'-propyl-1H,3'H-2,5'-bibenzo[d]imidazol-3'-yl)methyl)-6H-benzo[c]chromen-6-one, which was verified through (1)H LC-NMR experiments.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Benzimidazóis/química , Benzoatos/química , Cromatografia Líquida de Alta Pressão/métodos , Espectroscopia de Ressonância Magnética/métodos , Espectrometria de Massas/métodos , Deutério , Estabilidade de Medicamentos , Fotólise , Telmisartan
11.
J Pharm Biomed Anal ; 52(3): 406-9, 2010 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-19540696

RESUMO

Ayurvedic/herbal healthcare products are considered safe under the impression that they are derived from natural products. But recently, there have been several reports worldwide on the adulteration of synthetic PDE-5 inhibitors in aphrodisiac herbal formulations. Therefore, the objective of the present study was to explore the presence of synthetic PDE-5 inhibitors (sildenafil, tadalafil and/or vardenafil) in ayurvedic/herbal healthcare products sold in Indian market for aphrodisiac/related uses. In total, 85 herbal formulations (HFs) were included in the study. The formulations were extracted with methanol and subjected to centrifugation. The supernatant was analysed by HPLC and LC-MS/TOF. Early detection of the presence of sildenafil, tadalafil and vardenafil in the herbal samples was done by the study of extracted ion mass chromatograms at the m/z values of respective parent ions, and two prominent fragments of each. In case of sildenafil and tadalafil, adulteration was also detected by comparing the relative retention times (RR(T)) and UV spectra. Further substantiation was done through comparison of accurate mass spectra with those of the two available standards. Of the 85 HFs tested, only one was eventually found to be adulterated with sildenafil. The extent of adulterant in this sample was determined to the therapeutic dose in the formulation. The study thus indicates emergence of the problem of adulteration of Indian herbal products with PDE-5 inhibitors.


Assuntos
Afrodisíacos/análise , Cromatografia Líquida/métodos , Contaminação de Medicamentos , Inibidores de Fosfodiesterase/análise , Preparações de Plantas/análise , Espectrometria de Massas por Ionização por Electrospray/métodos , Carbolinas , Humanos , Imidazóis , Índia , Masculino , Espectrometria de Massas/métodos , Medicina Ayurvédica , Piperazinas , Purinas , Padrões de Referência , Reprodutibilidade dos Testes , Citrato de Sildenafila , Sulfonas , Tadalafila , Triazinas , Dicloridrato de Vardenafila
12.
J Pharm Biomed Anal ; 52(3): 332-44, 2010 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-19520540

RESUMO

The present study deals with the stress degradation studies on amorphous and polymorphic forms of clopidogrel bisulphate. The objective was to characterize the degradation products and postulate mechanism of decomposition of the drug under solid state stress conditions. For that, amorphous form, polymorph I and polymorph II of the drug were exposed to 40 degrees C/75% relative humidity (RH), with and without stressors for 3 months. The samples were analyzed by HPLC, and the relative extent of degradation as well as nature of decomposition was compared among three solid forms. In total, eight degradation products were observed under various stress conditions. The structures of all of them were elucidated using LC-MS/TOF and LC-MS(n) studies. While one matched the known hydrolytic decomposition product of the drug in solution, seven others were new. The postulated degradation pathway and mechanism of decomposition are discussed.


Assuntos
Inibidores da Agregação de Plaquetas/química , Ticlopidina/análogos & derivados , Cromatografia Líquida de Alta Pressão/métodos , Cromatografia Líquida/métodos , Clopidogrel , Simulação por Computador , Formas de Dosagem , Estabilidade de Medicamentos , Temperatura Alta , Concentração de Íons de Hidrogênio , Hidrólise , Luz , Espectrometria de Massas/métodos , Estrutura Molecular , Oxirredução , Fotólise/efeitos da radiação , Inibidores da Agregação de Plaquetas/análise , Reprodutibilidade dos Testes , Tecnologia Farmacêutica , Ticlopidina/análise , Ticlopidina/química , Fatores de Tempo , Difração de Raios X/métodos
13.
J Pharm Biomed Anal ; 51(5): 1037-46, 2010 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-20018473

RESUMO

Irbesartan was subjected to hydrolytic, oxidative, photolytic and thermal stress, according to ICH guideline Q1A (R2). The drug showed degradation only in acidic, basic and photoacidic conditions, while it was stable to other stress conditions. A total of three degradation products were formed, which were separated on a C-8 column employing a gradient HPLC method. Initially, a complete mass fragmentation pathway of the drug was established with the help of MS/TOF, MS(n) and H/D exchange studies. Subsequently, the degradation products were subjected to LC-MS/TOF and on-line H/D exchange mass studies to obtain their accurate mass, fragment pattern and number of labile hydrogens. The MS results helped to assign tentative structures to degradation products, which were verified through (1)H and 2D COSY LC-NMR experiments. The products were identified as (2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methanamine, 1-(1-((2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methylamino)pentylideneamino)cyclopentane carboxylic acid and 2-butyl-3-(tetrazolo[1,5-f]phenanthridin-6-ylmethyl)-1,3-diazaspiro[4.4]non-1-en-4-one. The structures were justified by mechanisms of their formation.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Compostos de Bifenilo/química , Cromatografia Líquida , Medição da Troca de Deutério , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Tecnologia Farmacêutica/métodos , Tetrazóis/química , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Hidrólise , Irbesartana , Modelos Químicos , Estrutura Molecular , Oxirredução , Fotólise , Temperatura
14.
J Pharm Biomed Anal ; 52(3): 345-54, 2010 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-19505786

RESUMO

Stress degradation studies were conducted on candesartan cilexetil under the ICH prescribed conditions of hydrolysis (acidic, basic and neutral), photolysis, oxidation and thermal stress. Maximum degradation was observed on hydrolysis, especially in the neutral condition. The drug was also degraded significantly under photolytic conditions. However, it was stable to oxidative and thermal stress. A total of eight degradation products were formed, the separation of which was successfully achieved on a C-18 column employing a gradient method. In order to characterize each degradation product, a complete mass fragmentation pathway of the drug was initially established with the help of MS(n) and MS/TOF accurate mass studies. Subsequently, degradation products were also subjected to LC-MS/TOF investigations, which resulted in their fragmentation pattern and also accurate masses. The latter helped in the elucidation of the structure of all the degradation products, which was achieved through comparison of their fragmentation pattern with that of the drug. The major product was isolated and its structure was confirmed through NMR studies. On the whole, a more comprehensive fragmentation behaviour and degradation profile of the drug was established than reported in the literature.


Assuntos
Bloqueadores do Receptor Tipo 1 de Angiotensina II/análise , Bloqueadores do Receptor Tipo 1 de Angiotensina II/química , Benzimidazóis/análise , Benzimidazóis/química , Compostos de Bifenilo/análise , Compostos de Bifenilo/química , Cromatografia Líquida/métodos , Espectrometria de Massas/métodos , Tetrazóis/análise , Tetrazóis/química , Química Farmacêutica/métodos , Estabilidade de Medicamentos , Concentração de Íons de Hidrogênio , Hidrólise , Espectroscopia de Ressonância Magnética , Estrutura Molecular , Peso Molecular , Oxirredução , Fotólise , Espectroscopia de Infravermelho com Transformada de Fourier
15.
J Pharm Biomed Anal ; 49(4): 880-8, 2009 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-19217740

RESUMO

A study was carried out to investigate compatibility of atenolol, a beta(1) blocker, with a variety of pharmaceutical excipients. The binary mixtures (1:1) of atenolol with the excipients were stored for 1 month at 40 degrees C/75% RH. The samples were directly observed for the physical changes, and also analyzed by a validated HPLC method to determine the chemical changes. The study revealed that atenolol was incompatible with ascorbic acid, citric acid and butylated hydroxyanisole. The degradation/interaction products formed in these mixtures were characterized by high resolution mass spectrometric and fragmentation analyses, using a LC-MS/TOF system. The identity of characterized structures was justified through mechanistic explanations.


Assuntos
Antagonistas Adrenérgicos beta/química , Atenolol/química , Ácido Ascórbico/química , Hidroxianisol Butilado , Cromatografia Líquida de Alta Pressão , Ácido Cítrico/química , Incompatibilidade de Medicamentos , Excipientes/química , Concentração de Íons de Hidrogênio , Indicadores e Reagentes , Espectrometria de Massas , Excipientes Farmacêuticos , Espectrofotometria Ultravioleta
16.
J Pharm Biomed Anal ; 47(3): 508-15, 2008 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-18343073

RESUMO

"Polypill" is a fixed-dose combination (FDC) containing three or more drugs in a single pill. The same is under development for the treatment and prevention of cardiovascular diseases. In the present study, gradient LC methods were developed for simultaneous determination of the possible components of a polypill, i.e., lisinopril, aspirin and one each among atenolol/hydrochlorothiazide and atorvastatin/simvastatin/pravastatin, in the presence of a total of 13 major interaction/degradation products. The drugs and the products were well separated using a reversed-phase (C-8) column and a mobile phase comprising of acetonitrile: phosphate buffer (pH 2.3). Other HPLC parameters were flow rate, 1 ml/min; detection wavelength, 210 nm; column oven temperature, 60 degrees C; and injection volume, 5 microl. The methods were validated for linearity, precision, accuracy, and specificity. These were further modified to make them compatible for LC-MS studies by removal of the phosphate buffer and adjustment of pH by formic acid. The suitability of the methods for LC-MS studies was established by matching the theoretical mass values of the drugs with those obtained experimentally. These methods were used to determine mass values of the major interaction/degradation products, which helped to know the source of their origin.


Assuntos
Fármacos Cardiovasculares/análise , Cromatografia Líquida de Alta Pressão/métodos , Combinação de Medicamentos , Espectrometria de Massas por Ionização por Electrospray/métodos , Aspirina/análise , Atenolol/análise , Atorvastatina , Interações Medicamentosas , Estabilidade de Medicamentos , Ácidos Heptanoicos/análise , Hidroclorotiazida/análogos & derivados , Hidroclorotiazida/análise , Lisinopril/análise , Pravastatina/análise , Pirróis/análise , Sinvastatina/análise
17.
Rapid Commun Mass Spectrom ; 22(5): 613-22, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18247406

RESUMO

A comprehensive mass fragmentation pathway of atorvastatin, which has not been reported so far, was established by subjecting the drug to multi-stage mass spectrometric (MSn) studies. It was used along with liquid chromatography/mass spectrometric (LC/MS) and liquid chromatography/time-of-flight mass spectrometric (LC/TOFMS) analyses to identify the drug degradation products formed under stress conditions of hydrolysis, oxidation and photolysis. Other than lactone, which is a reported hydrolysis product, six unknown hydrolytic products could be identified, viz., dehydrated drug, dehydrated drug lactone, and diastereomers of the drug, drug lactone, dehydrated drug, and dehydrated drug lactone. Among the two products separated under oxidative conditions, one was lactone, again formed as a result of drug hydrolysis in an acidic environment of peroxide solution. The other was similar to a reported oxidative product. Under photolytic conditions in solution, one new product could be identified, while most of the others matched with those known from the literature. Hence overall a more complete degradation pathway of the drug was established than known at present, by using a stress testing approach and employing LC/MS techniques.


Assuntos
Anticolesterolemiantes/química , Ácidos Heptanoicos/química , Inibidores de Hidroximetilglutaril-CoA Redutases/química , Pirróis/química , Espectrometria de Massas por Ionização por Electrospray/métodos , Atmosfera , Atorvastatina , Cromatografia Líquida de Alta Pressão , Hidrólise , Luz , Estrutura Molecular , Oxirredução , Fotoquímica , Fotólise/efeitos da radiação
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