Profiles of drug substances, excipients, and related methodology最新文献

Valsartan is an antihypertensive drug which selectively inhibits angiotensin receptor type II. Generally, valsartan is available as film-coated tablets. This review summarizes thermal analysis, spectroscopy characteristics (UV, IR, MS, and NMR), polymorphism forms, impurities, and related compounds of valsartan. The methods of analysis of valsartan in pharmaceutical dosage forms and in biological fluids using spectrophotometer, CE, TLC, and HPLC methods are discussed in details. Both official and nonofficial methods are described. It is recommended to use LC-MS method for analyzing valsartan in complex matrices such as biological fluids and herbal preparations; in this case, MRM is preferred than SIM method.

Losartan (Cozaar™) is an angiotensin II receptor antagonist with antihypertensive activity. It is used in the management of hypertension and heart failure. Nomenclature, formulae, elemental analysis, and appearance of the drug are included in this review. The uses, applications, and the variety of synthetic pathways of this drug are outlined. Physical characteristics including: ionization constant, solubility, X-ray powder diffraction pattern, thermal methods of analysis, UV spectrum, IR spectrum, mass spectrum with fragmentation patterns, and NMR (1H and 13C) spectra of losartan together with the corresponding figures and/or tables are all produced. This profile also includes the monograph of British Pharmacopoeia, together with several reported analytical methods including: spectrophotometric, electrochemical, chromatographic, and capillary electrophoretic methods. The stability, the pharmacokinetic behavior and the pharmacology of the drug are also provided.

Cinnarizine is a piperazine derivative with antihistaminic, antiserotonergic, antidopaminergic, and calcium channel-blocking activities. A comprehensive profile was performed on cinnarizine including its description and the different methods of analysis. The 1H NMR and 13C one- and two-dimensional NMR methods were used. In addition, infrared and mass spectral analyses were performed which all confirmed the structure of cinnarizine.

Salmeterol xinafoate is a potent and a long-acting β2-adrenoceptor agonist. It is prescribed for the treatment of severe persistent asthma and chronic obstructive pulmonary disease. Different methods were used to prepare (R)-(-)-salmeterol such as: mixing a sample of 4-benzyloxy-3-hydroxymethyl-ω-bromoacetophenone with sodium lauryl sulfate and the mixture was added to the microbial culture of Rhodotorula rubra, treatment of p-hydroxyacetophenone with Eschenmoser's salt and carbonate exchange resin followed by a sequence of supported reagents and scavenging agents or via Rh-catalyzed asymmetric transfer hydrogenation. The enantioselective synthesis of (S)-salmeterol was achieved via asymmetric reduction of the azidoketone 4 by Pichia angusta yeast. Physical characteristics of salmeterol xinafoate were confirmed via: X-ray powder diffraction pattern, thermal analysis and UV, vibrational, nuclear magnetic resonance, and mass spectroscopical data. Initial improvement in asthma control may occur within 30 min following oral inhalation of salmeterol in fixed combination with fluticasone propionate. Clinically important improvements are maintained for up to 12 h in most patients. It is extensively metabolized in the liver by hydroxylation, thus increased plasma concentrations may occur in patients with hepatic impairment.

A comprehensive profile of prasugrel HCl is reported herein with 158 references. A full description including nomenclature, formulae, elemental analysis, and appearance is included. Methods of preparation for prasugrel HCl, its intermediates, and derivatives are fully discussed. In addition, the physical properties, analytical methods, stability, uses and applications, and pharmacology of prasugrel HCl are also discussed.

Telmisartan is an angiotensin-II receptor antagonist (ARB) used in the treatment of hypertension. Generally, angiotensin-II receptor blockers such as telmisartan bind to the angiotensin-II type 1 receptors with high affinity, causing inhibition of the action of angiotensin II on vascular smooth muscle, ultimately leading to a reduction in arterial blood pressure. The present study gives a comprehensive profile of telmisartan, including detailed nomenclature, formulae, elemental analysis, and appearance of the drug are mentioned. The uses and applications and the several methods described for its preparation of the drug are outlined. The profile contains the physicochemical properties including: pKa value, solubility, X-ray powder diffraction, melting point, and methods of analysis (including compendial, electrochemical, spectroscopic, and chromatographic methods of analysis). Developed validated stability-indicating (HPLC and biodiffusion assay methods under accelerated acidic, alkaline, and oxidative conditions, in addition to effect of different types of light, temperature, and pH. Detailed Pharmacology also presented (Pharmacological actions, Therapeutic uses and Dosing, Interactions, and adverse effects and precautions). More than 80 references were given as a proof of the above-mentioned studies.

Glutathione is an endogenous peptide with antioxidant and other metabolic functions. The nomenclature, formulae, elemental composition, and appearance and uses of the drug are included. The methods used for the synthesis and biosynthesis of glutathione are described. This profile contains the physical characteristics of the drug including: solubility, X-ray powder diffraction pattern, crystal structure, melting point, and differential scanning calorimetry. The spectral methods that were used for both the identification and analysis of glutathione include ultraviolet spectrum, vibrational spectrum, 1H and 13C nuclear magnetic resonance spectra, and mass spectrum. The profile also includes the compendial methods of analysis and the other methods of analysis that are reported in the literature. These other methods of e-analysis are: potentiometric, voltammetric, amperometric, spectrophotometric, specrtofluorometric, chemiluminescence, chromatographic and immunoassay methods. The stability of and several reviews on drug are also provided. More than 170 references are listed at the end this comprehensive profile on glutathione.

Dasatinib (Sprycel®), a second-generation TKI, has been shown to be effective as an anticancer drug in the treatment of patients with chronic myeloid leukemia or Philadelphia chromosome-positive acute lymphoblastic leukemia who are resistant or intolerant to imatinib. Several methods of gefitinib synthesis are included in this review. UV spectroscopy of dasatinib showed a λmax of approximately 320-330nm, and IR spectroscopy principal peaks were observed at 3418 (NH), 3200 (OH), 1620 (CO), 1582 (CC and CN), 1513 (CHCH) cm(-1). Characteristic NH peaks were observed in nuclear magnetic resonance (NMR) spectroscopy at 11.47 and 9.88ppm. The molecular mass was observed at m/z=487.3((35)Cl) and 488.9((37)Cl) (molecular weight=487.15) and the fragmentation pattern was studied using ion trap mass spectrometry. In addition, different analytical methods for determination of dasatinib are also described in this review. Pharmacokinetically, dasatinib is rapidly absorbed after oral administration where the solubility is dependent on pH. Dasatinib extensively binds to human plasma proteins by approximately 96%. In leukemic patient, the calculated apparent volume of distribution for dasatinib was 2502L and the estimated elimination half-life was approximately 3-5h. Dasatinib is metabolized in humans markedly by CYP3A4 to active metabolites and by phase II drug-metabolizing enzymes, such as UDP glucuronosyltransferase. Dasatinib is mainly eliminated via the feces (85%), of which relatively small amount of dasatinib is excreted unchanged as intact drug (19%). Most of the adverse effects associated with dasatinib therapy are mild to moderate in severity and are usually reversible and manageable with appropriate intervention, such as cardiac failure, hypertension, and coronary artery disease.