Abstract：
:A multidisciplinary team approach to identify pharmaceutical impurities is presented in this article. It includes a representative example of the methodology. The first step is to analyze the sample by LC-MS. If the structure of the unknown impurity cannot be conclusively determined by LC-MS, LC-NMR is employed. If the sample is unsuitable for LC-NMR, the impurity needs to be isolated for conventional NMR characterization. Although the technique of choice for isolation is preparative HPLC, enrichment is often necessary to improve preparative efficiency. One such technique is solid-phase extraction. For complete verification, synthesis may be necessary to compare spectroscopic characteristics to those observed in the original sample. Although not widely practiced, an effective means of getting valuable structural information is to conduct a degradation study on the purified impurity itself. This systematic strategy was successfully applied to the identification of an impurity in the active pharmaceutical ingredient 1-(1,2,3,5,6,7-hexahydro-s-indacen-4-yl)-3-[4-(1-hydroxy-1-methyl-ethyl)-furan-2-sulphonylurea. Identification required the use of all of the previously mentioned techniques. The instability of the impurity under acidic chromatographic conditions presented an additional challenge to purification and identification. However, we turned this acidic instability to an advantage, conducting a degradation study of the impurity, which provided extensive and useful information about its structure. The following discussion describes how the information gained from each analytical technique was brought together in a complementary fashion to elucidate a final structure.
journal_name
J Pharm Scijournal_title
Journal of pharmaceutical sciencesauthors
Alsante KM,Boutros P,Couturier MA,Friedmann RC,Harwood JW,Horan GJ,Jensen AJ,Liu Q,Lohr LL,Morris R,Raggon JW,Reid GL,Santafianos DP,Sharp TR,Tucker JL,Wilcox GEdoi
10.1002/jps.20120subject
Has Abstractpub_date
2004-09-01 00:00:00pages
2296-309issue
9eissn
0022-3549issn
1520-6017pii
S0022-3549(16)31594-5journal_volume
93pub_type
杂志文章abstract：:A novel technique is presented to allow measurement of the kinetics of protein inactivation during drying of an acoustically levitated single droplet. Droplets/particles are removed from the acoustic field after various times during drying, and the state of the protein within them is analyzed. The influence of drying ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.23129
更新日期：2012-06-01 00:00:00
abstract：:A study of the pH of saliva produced by humans sucking hard candy lozenges containing zinc gluconate and citric acid demonstrated the probability that the formulation delivered an insignificant amount of the contained zinc as Zn2+. This could account for the negative results of several clinical studies of this lozenge...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600810205
更新日期：1992-02-01 00:00:00
abstract：:Ethylene oxide (EtO) is widely used in sterilization of drug product primary containers and medical devices. The impact of residual EtO on protein therapeutics is of significant interest in the biopharmaceutical industry. The potential for EtO to modify individual amino acids in proteins has been previously reported. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24257
更新日期：2015-02-01 00:00:00
abstract：:A specific and reproducible high-performance liquid chromatographic (HPLC) procedure was developed for the quantitative analysis of carboplatin (JM-8) in dog plasma ultrafiltrate. Plasma ultrafiltrate samples were generated using Amicon Centrifree micropartition systems or Amicon Centriflo cones, and injected onto a m...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600770318
更新日期：1988-03-01 00:00:00
abstract：:The in vitro antifungal activity of a novel series of cis- and trans-5-([aryl or aryloxy (or thio)]methyl)-3-(1H-imidazol-1-ylmethyl)-3- (2-thienyl)-2-methylisoxazolidines (13-24) was evaluated and compared with ketoconazole. The title series of compounds was prepared via a 1,3-dipolar cycloaddition reaction of 1-(2-t...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600771213
更新日期：1988-12-01 00:00:00
abstract：:Capillary gas chromatography using an open tubular fused silica column and NP-FID was applied to the simultaneous analysis of the antihistamine, carbinoxamine, and the antitussive, hydrocodone, in human serum. Carbinoxamine and hydrocodone were extracted into methylene chloride-2-propanol (9:1) under alkaline conditio...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600721126
更新日期：1983-11-01 00:00:00
abstract：:Melphalan (30 microgram/ml) is completely hydrolyzed in water at 37 degrees after 8 hr. At lower temperatures, hydrolysis proceeds at slower rates. The presence of bovine serum albumin retards hydrolysis of melphalan (30 microgram/ml) in water. The melphalan hydrolysis rate is directely releated to the bovine serum al...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670530
更新日期：1978-05-01 00:00:00
abstract：:The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentrat...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20081
更新日期：2004-07-01 00:00:00
abstract：:Taraxacum mongolicum (TM), also known as dandelion, is a herb widely used in the East for its antibacterial activity. The high mineral content of TM presents a potential problem for the absorption of quinolone antibiotics. This study was undertaken to discern the significance of a drug-drug interaction between TM and ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js980367q
更新日期：1999-06-01 00:00:00
abstract：:The aim was to study a new method of dissolution in vitro, the "Bio-Dis" apparatus, and to compare it with the classical rotating bottle method. Several theophylline controlled-release drug dosage forms were studied. Dissolution testing was performed in increasing pH in standard conditions and after treatment with pea...
journal_title：Journal of pharmaceutical sciences
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1002/jps.2600801017
更新日期：1991-10-01 00:00:00
abstract：:The present study was conducted to investigate the impact of drying method and formulation on the storage stability of IgG1. Formulations of IgG1 with varying levels of sucrose with and without surfactant were dried by different methods, namely freeze drying, spray drying, and foam drying. Dried powders were character...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.20859
更新日期：2007-08-01 00:00:00
abstract：:Fibril formation (aggregation) of human and bovine insulin and six human insulin mutants in hydrochloric acid were investigated by visual inspection, Thioflavin T fluorescence spectroscopy, transmission electron microscopy (TEM), and Fourier transform infrared (FTIR) spectroscopy. The fibrillation tendencies of the wi...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.10238
更新日期：2002-12-01 00:00:00
abstract：:Controlling residual solvent levels is a major concern in pharmaceutical freeze-drying from co-solvent systems. This review provides an overview of the factors influencing this process and estimates their potential to reduce residual solvents in freeze-dried products. Decreased solvent contents are potentially correla...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章,评审
doi：10.1016/j.xphs.2018.04.001
更新日期：2018-08-01 00:00:00
abstract：:Hexamidine isethionate in various pharmaceutical formulations was analyzed quantitatively by high-performance liquid chromatography. The method is rapid, accurate, and precise. Excellent results were obtained from four commercial bases. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600721229
更新日期：1983-12-01 00:00:00
abstract：:This study aims to investigate the drug-drug interactions (DDIs) between orally administered atorvastatin (ATV) and rifampicin (RIF) in rats. The isotope-IV method was used for the analysis of the increased systemic exposure (AUCpo) of ATV, in which a small amount of deuterium-labeled ATV (ATV-d5) was intravenously in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1016/j.xphs.2017.04.027
更新日期：2017-09-01 00:00:00
abstract：:A Bayesian approach was developed to determine an amikacin dosage regimen to achieve the desired plasma concentrations for each patient. Statistical characteristics of pharmacokinetic parameters were first evaluated in a group of patients (reference population), which when combined with three individual plasma concent...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600780911
更新日期：1989-09-01 00:00:00
abstract：:Substance P (SP) was degraded by synaptic membranes of rat spinal cord. Cleavage products were separated by reversed phase high performance liquid chromatography and identified by amino acid composition analyses. Major products of SP were phenylalanine, SP(1-4), SP(1-6), SP(1-7), SP(10-11), and SP(8-9). Both the degra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js990149c
更新日期：1999-11-01 00:00:00
abstract：:A new method for determining a quaternary mixture of vitamins B6, B1, and B12 and uridine 5'-triphosphate (UPT) using second-derivative spectrophotometry is described. Calibration graphs were linear up to 30 micrograms/mL of vitamin B6 at 307 nm (r = 0.9999) and vitamin B1 at 282.7 nm (r = 0.9997) and up to 35 microgr...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840109
更新日期：1995-01-01 00:00:00
abstract：:This study was designed to examine the effect of benzalkonium chloride/ethylenediaminetetraacetic acid (BAK/EDTA) on the ocular bioavailability (Focular) of ketorolac tromethamine after ocular instillation to normal and de-epithelialized corneas of rabbits both in vitro and in vivo. The in vitro Focular of the formula...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1021/js9504189
更新日期：1996-04-01 00:00:00
abstract：:The crystal and molecular structures of 6-methylmercaptopurine trihydrate and of azathioprine dihydrate were determined by the use of three-dimensional, X-ray, diffractometer data and were refined by least squares. Both molecules crystallize in the N(9)-H tautomer form, in contrast to the N(7)-H tautomer form found in...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600640206
更新日期：1975-02-01 00:00:00
abstract：:Currently, the EMEA, FDA, and WHO as regulatory authorities accept rapidly dissolving (>85% dissolved in 30 min) biopharmaceutics classification system (BCS) I drug products for biowaiver candidates. In the draft EMEA guideline the requirement has been set tighter, that is, the drug product should be very rapidly diss...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21879
更新日期：2010-02-01 00:00:00
abstract：:Chloroquine (7-chloro-4-[[4-(diethylamino)-1-methylbutyl]amino]quinoline; CQ) accumulates in the insoluble fraction of rat muscle homogenates with an equilibrium distribution ratio of 7.8 L/kg. This is of a similar magnitude to muscle:plasma ratios observed in vivo. Uptake is approximately linear, even up to concentra...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600751109
更新日期：1986-11-01 00:00:00
abstract：:Aqueous solutions of several ionizable substances were stored in plastic infusion bags and the sorption of the substances monitored with time. The substances used were p-nitrophenol, p-toluidine, warfarin sodium [3-(alpha-acetonylbenzyl)-4-hydroxycoumarin sodium salt] and trifluoperazine hydrochloride (10-[3-(4-methyl...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600750608
更新日期：1986-06-01 00:00:00
abstract：:Judicious choice of the salt form of a drug can greatly affect the aqueous solubility and formulation of the compound. The objective of this work was to demonstrate the effect of various counteranions on the aqueous solubility of the antimalarial agent alpha-(2-piperidyl)-3, 6-bis(trifluoromethyl)-9-phenanthrenemethan...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650533
更新日期：1976-05-01 00:00:00
abstract：:The central compartment of an n-compartment mammillary model was concatenated with a gradient compartment (i.e., venous sampling compartment) and with a conventional effect compartment to model arterial-venous drug concentration gradients and the arterial drug concentration vs effect relationship, respectively. To mod...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600840320
更新日期：1995-03-01 00:00:00
abstract：:Digoxin binding to normal and kwashiorkor serum was studied and found to be inferior in the latter. Digoxin should be used with care in hypoalbuminemic patients. ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600650629
更新日期：1976-06-01 00:00:00
abstract：:Volunteers were injected im with 100 mg of tripelennamine (pyribenzamine).HCl dissolved in saline. Timed urine was collected. Tripelennamine and its metabolites were identified by GC/MS. Amounts of free tripelennamine excreted in the 0-2-, 2-4-, 4-8-, 8-12-, and 12-24-h urine samples were found to be 0.30, 0.56, 0.17,...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600800902
更新日期：1991-09-01 00:00:00
abstract：:To explore the possibility of cyclodextrin click clusters (CCCs) as a new cyclodextrin-based excipient, we prepared three different CCCs; heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}-β-cyclodextrin (HT-β-CD), heptakis{6-(4-hydroxymethyl-1H-[1,2,3]triazol-1-yl)-6-deoxy}{2,3-di-O-methyl}-β-cyclodextrin (...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.24107
更新日期：2014-10-01 00:00:00
abstract：:Transformation of polymorph I of clopidogrel hydrogen sulfate (CHS) to polymorph II of CHS during the crystallization was monitored by using in situ measurement of ultrasonic velocity. Drowning-out crystallization using methanol as a solvent and isopropyl alcohol as nonsolvent was carried out. The polymorphs were iden...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.21313
更新日期：2008-10-01 00:00:00
abstract：:The extent of formation of solasodiene from solasodine upon treatment with hydrochloric acid under various conditions was determined. The diene formed was assayed by using the characteristic extinction at 236 nm. Diene formation was effected by the acid concentration and the boiling point of the solvent used. Optimal ...
journal_title：Journal of pharmaceutical sciences
pub_type： 杂志文章
doi：10.1002/jps.2600670839
更新日期：1978-08-01 00:00:00
