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PubMed1978

Electrochemical properties of polycyclic compounds studied by the polarographic method in anhydrous systems. VI. The influence of proton-donor on reduction of carcinogenic aromatic hydrocarbons in anhydrous environment.

The authors have studied the electrochemical behaviour of a series of carcinogenic and inactive aromatic hydrocarbons in anhydrous environment in the presence of a proton-donor. As anhydrous environment the authors used water-free dimethylformamide and dimethylsulfoxide; as proton-donor phenol. Phenol gave rise to quantitative changes in the number of polarographic waves when the carcinogenic aromatic hydrocarbons were undergoing reduction. Between the two original waves there originated in the presence of phenol a new polarographic wave in these hydrocarbons. In inactive analogues of the investigated hydrocarbons no such effect of phenol has been ascertained. In their present study the authors discuss the potential mechanism of electroreduction of carcinogenic and inactive aromatic hydrocarbons in anhydrous environment in the presence of a proton-donor and compare the values of half-wave potentials of the investigated compounds measured in water-free dimethylformamide, dimethylformamide + phenol and in ethylenglycolmonomethylether.

Carcinogens↗

PubMed1993

Hepatic CYP1A1 induction in rainbow trout by continuous flowthrough exposure to beta-naphthoflavone.

In order to assess the usefulness of CYP1A1 mRNA measurement as an environmental biomarker it was necessary to determine if hepatic P450 CYP1A1 mRNA induction is sustained during constant exposure to hepatic monooxygenase inducers. To accomplish this, rainbow trout (Oncorhynchus mykiss) were exposed, under flowthrough conditions, to beta-naphthoflavone (beta-NF), a known CYP1A1 inducer in fish. Trout were exposed to a beta-NF concentration of 1.0 mg beta-NF/liter, using dimethylformamide as carrier, for 1, 2, 4, and 8 days, followed by depuration in clean water for 1, 8, 14, and 35 days. In a second experiment, trout were exposed to beta-NF concentrations of 0.05, 0.10, and 0.50 mg beta-NF/liter, using dimethylformamide as carrier, for 1, 3, 7, and 14 days, followed by depuration for 7 and 28 days. At the 1.0-mg beta-NF/liter concentration, ethoxyresorufin-O-deethylase (EROD) activity was significantly decreased by 4 days of exposure when compared to controls. At beta-NF concentrations of 0.05 to 0.50 mg beta-NF/liter EROD activity was increased compared to controls but was inversely related to the beta-NF concentration. Hybridizable CYP1A1 mRNA was increased approximately 40-fold over control levels at concentrations of 0.05 to 0.50 mg beta-NF/liter for 1, 3, and 7 days of exposure. In a third experiment, trout exposed to 0.05 mg beta-NF/liter for 2, 6, 12, 24, 32, 40, and 48 hr had increased (45- to 167-fold) EROD activity by 18 and 48 hr, respectively. Immunoreactive CYP1A1 protein was increased 46-fold at 48 hr and CYP1A1 mRNA was increased 29-fold at 48 hr of continuous beta-NF exposure. This is in contrast to previous experiments using intraperitoneal injection of beta-NF in which the induced CYP1A1 mRNA decreased to near control levels by 48 hr after injection. These data indicate that both CYP1A1 catalytic activity and immunoreactive protein are decreased at high inducer concentrations while mRNA levels remain elevated and continue to increase over time during continuous exposure. In a fourth experiment trout were continuously exposed to concentrations of 0.625, 1.25, 2.5, 5.0, and 10.0 micrograms beta-NF/liter, using dimethylformamide as carrier, for 1, 3, 7, 14, and 21 days, followed by clean water depuration for 1, 3, 7, 14, and 21 days EROD activity was significantly increased in a concentration-dependent manner over control by Day 1 of exposure with concentrations of 2.5, 5.0, and 10.0 micrograms beta-NF/liter.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1977

[Azoindoxyl methods for the investigation of hydrolases. II. Biochemical and histochemical studies of acid beta-galactosidase (author's transl)].

The determination of various reaction constants yields the following assay for the photometric evaluation of acid beta-galactosidase (measurement of the azoindoxyl dye at 540 nm after extraction with dimethylformamide or -acetamide): 1.5 mM 5-Br-4-Cl-3-indolyl-beta-D-galactoside (1 mg dissolved in 0.05 ml dimethylformamide) and 0.01-0.015 ml hexazotized p-rosaniline/ml in 0.1 M citric acid-phosphate buffer, pH 4. By means of this procedure it becomes evident that the activity of the enzyme differs considerably in various rat organs; NaCl does not influence acid beta-galactosidase. -- Similar results were obtained with the indigogenic method; indigo can be dissolved and measured photometrically as the azoindoxyl dye. The enzyme is suppressed by high concentrations of hexazotized p-roaniline to 50%; low concentrations do not inhibit; the same is true for ferricyanide-ferrocyanide employed in the indigogenic media. -- The effect of glutar- and formaldehyde on acid beta-galactosidase cannot be investigated with the azoindoxyl reaction since the azoindoxyl dye partially withstands extraction from fixed blocks of tissue. On the basis of the biochemical findings the azoindoxyl technique can be recommended for the histochemical demonstration of acid beta-galactosidase: 7.5 mg (1.5 mM) 5-Br-4-Cl-3-indolyl-beta-D-galactoside (dissolved in 0.25 ml dimethylformamide) and 0.05-0.15 ml hexazonium-p-rosaniline in 10 ml 0.1 M citric acid-phosphate buffer, pH 4. After incubation the sections can be treated with osmium tetroxide followed by dehydration and mounting in resins or can be mounted without prior osmification of the azoindoxyl dye in glycerin jelly. The osmium chelate resists treatment with organic solvents; the stability of the chelate depends on the concentration of hexazotized p-rosaniline. After fixation in glutaraldehyde or in a mixture of form- and glutaraldehyde acid beta-galactosidase can be exactly localized in the lysosomes of many rat organs. In comparison with the indigogenic, the metal precipitation and the simultaneous azocoupling reactions for the in situ detection of acid beta-galactosidase the azoindoxyl procedure is superior if fixed material is used; it is equivalent or inferior in connection with membrane technique. The biochemical azoindoxyl assay represents a useful method for combined qualitative and quantitative studies of acid beta-galactosidase.

Aldehydes↗

PubMed2006

Sensitization of photo-reduction of the polyoxometalate anions [S(2)M(18)O(62)](4-) (M = Mo, W) in the visible spectral region by the [Ru(bpy)(3)](2+) cation.

Voltammetric, photo-physical and photo-electrochemical properties of the Dawson polyoxometalate anions alpha-[S(2)M(18)O(62)](4-) (M = Mo, W) are presented, both in the presence and absence of a series of [Ru(II)L(n)](+/2+) cations [L(n) = (bpy)(3), (bpy)(2)(Im)(2), (bpy)(2)(dpq), (bpy)(2)(box) and (biq)(2)(box)]. Electrochemical processes for both the anion and Ru(II/III) couples were detected in solutions of the salts [Ru(II)L(n)](2)[S(2)M(18)O(62)] in dimethylformamide (0.1 M Bu(4)NPF(6)) by both cyclic and hydrodynamic voltammetries. Responses were also detected when the solid salts were adhered to the surface of a glassy carbon electrode in contact with an electrolyte in which they are insoluble (CH(3)CN; 0.1M Bu(4)NPF(6)). Photolysis experiments were performed on solutions of the salts [R(4)N](4)[S(2)M(18)O(62)] (R = n-butyl or n-hexyl) and [Ru(II)L(n)](2)[S(2)M(18)O(62)] at 355 and 420 nm in dimethylformamide and acetonitrile in the presence and absence of benzyl alcohol (10% v/v). When associated with [Ru(bpy)(3)](2+), the molybdate anion exhibited a large increase in the quantum yield for photo-reduction at 420 nm. The quantum yield for the tungstate analogue was lower but the experiments again provided clear evidence for sensitization of the photo-reduction reaction in the visible spectral region. The origin of this sensitization is ascribed to the new optical transition observed around 480 nm in static ion clusters {[Ru(bpy)(3)][S(2)M(18)O(62)]}(2-) and {[Ru(bpy)(3)](2)[S(2)M(18)O(62)]} present in solution. Measurable photocurrents resulted from irradiation of solutions of the anions with white light in the presence of the electron donor dimethylformamide. Evidence is also presented for possible quencher-fluorophore interactions in the presence of certain [Ru(II)L(n)](+) cations.

Anions↗

PubMed2005

Cyano-bridged extended heteronuclear supramolecular architectures with hexacyanocobalt(III) as building blocks.

The cyano-bridged heteronuclear coordination polymer poly[tris[(5,12-dimethyl-7,14-diphenyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene)copper(II)]-hexa-mu-cyano-bis[tricyanocobalt(III)] dimethylformamide solvate trihydrate], {[Cu3Co2(CN)12(C24H32N4)3].C3H7NO.3H2O}n, was synthesized by the assembly reaction of [CuL]2+ (L is 5,12-dimethyl-7,14-diphenyl-1,4,8,11-tetraazacyclotetradeca-4,11-diene) and [Co(CN)6]3- in a dimethylformamide-water solution. The structure consists of neutral cyano-bridged Cu3Co2 units with the unique Co atom in a general position and all three Cu atoms on independent inversion centres. Each [Co(CN)6]3- ion connects three CuII ions via three cyano groups to form a novel cyano-bridged two-dimensional stair-shaped-layer structure. The water and dimethylformamide molecules are situated in the inter-fragment spaces.

Journal Article↗

PubMed2004

Preparation and physicochemical characterization of 5 niclosamide solvates and 1 hemisolvate.

The purpose of the study was to characterize the physicochemical, structural, and spectral properties of the 1:1 niclosamide and methanol, diethyl ether, dimethyl sulfoxide, N,N' dimethylformamide, and tetrahydrofuran solvates and the 2:1 niclosamide and tetraethylene glycol hemisolvate prepared by recrystallization from these organic solvents. Structural, spectral, and thermal analysis results confirmed the presence of the solvents and differences in the structural properties of these solvates. In addition, differences in the activation energy of desolvation, batch solution calorimetry, and the aqueous solubility at 25 degrees C, 24 hours, showed the stability of the solvates to be in the order: anhydrate > diethyl ether solvate > tetraethylene glycol hemisolvate > methanol solvate > dimethyl sulfoxide solvate > N,N' dimethylformamide solvate. The intrinsic and powder dissolution rates of the solvates were in the order: anhydrate > diethyl ether solvate > tetraethylene glycol hemisolvate > N,N' dimethylformamide solvate > methanol solvate > dimethyl sulfoxide solvate. Although these nonaqueous solvates had higher solubility and dissolution rates than the monohydrous forms, they were unstable in aqueous media and rapidly transformed to one of the monohydrous forms.

Chemical Phenomena↗

PubMed1975

[Iodo-derivatives of 2-aminobenzensulfonamide and 1,2,4-benzothiadiazine-1,1-dioxide].

A series of iodo derivatives of 2-aminobenzensulfonamide and its derivatives has been prepared by reaction with iodine chloride in N,N-dimethylformamide or N,N-dimethylacetamide. The structure of each compound was confirmed by transformation with formic acid into the corresponding 1,2,4-benzothiadiazine and comparison with the same compounds prepared via the Sandmeyer reaction starting form amino derivatives of known structure. It was found that the iodination reaction in N,N-dimethylformamide, can lead, depending on the nature of the starting material, to the formation of benzothiadiazine derivatives apparently generated from sulfonamide via a formylation reaction due to N,N-dimethylformamide.

Benzene Derivatives↗

PubMed1975

[Study of the association of nystatin and amphotericin B in nonaqueous solvent systems].

Association of nystatin and amphotericin B in non-aqueous systems was studied with the method of equilibria dialysis. A specially treated celophane membrane arresting colloid associats and macromolecules with a molecular weight of more than 30000 in the systems of dimethylformamide-ethylacetate was used for the dialysis. Relation between the dialysis rate and the difference of the concentrations at every side of the membrane was used for estimation of the antibiotic colloid association level. It was found that nystatin formed stable associates of the colloid type in the system of dimethylformamide-ethylacetate, close by the composition to the critical one or that providing precipitation of the antibiotic. Unlike nystatin, amphotericin B formed not colloid but larger conglomerates which precipitated. Neither of the antibiotics formed colloid associates in dimethylformamide. The level of the nystatin colloid association increased with a rise in the solution concentration and reached 80%. On the basis of the results obtained the following supposition concerning the mechanism of formation of the antibiotic complexes with polyvinylpyrrolidone (PVP) in non-aqueous systems is possible: sorption of PVP on the colloids formed or larger associates of the polyenic antibiotics must take place during coprecipitation which is accompanied by formation of a precipitate of the sorption complex.

Amphotericin B↗

PubMed1987

Effects of difluoromethylornithine and dicyclohexylammonium sulfate on the transformed state of AKR-MCA cells.

The effect of two inhibitors of polyamine biosynthesis, difluoromethylornithine and dicyclohexylammonium sulfate, on the transformed fibroblastic cell line AKR-MCA and its parental counterpart AKR-2B was investigated. Treatment of monolayer AKR-MCA cells with either agent results in morphological changes akin to AKR-2B; the cells appear to be flattened with a polygonal shape. The ability of the inhibitors to alter the phenotype is lost when the cells are cocultured with polyamines. More specifically, putrescine and spermidine abrogate the effects of difluoromethylornithine while only spermidine is effective in reversing the dicyclohexylammonium sulfate induced phenomenon. Further evidence that these enzyme inhibitors are reversing the transformed state of AKR-MCA is obtained from soft agarose experiments. AKR-MCA cells will generate colonies only in the absence of either difluoromethylornithine or dicyclohexylammonium sulfate. Polyamine levels were determined in parental AKR-2B and AKR-MCA cells. The levels of putrescine and spermine were similar in both cell types. In contrast, significantly more (P less than or equal to 0.01) spermidine was expressed by the malignant line [7.3 +/- 0.8 (SD) nmol/10(6) cells] when compared with the untransformed AKR-2B (5.4 +/- 0.8 nmol/10(6)) cells. Intracellular putrescine and spermidine were sensitive to difluoromethylornithine, dicyclohexylammonium sulfate, and dimethylformamide, a planar, polar solvent which has been reported to "normalize" the transformed phenotype. AKR-MCA treated with difluoromethylornithine or dimethylformamide manifested time dependent reductions in both polyamines which preceded morphological changes. Dicyclohexylammonium sulfate similarly caused a 70% reduction in spermidine, but in contrast to the other agents there was a marked accumulation of putrescine. These data concur with the established molecular actions of the two enzyme inhibitors as blockers of ornithine decarboxylase (difluoromethylornithine) and spermidine synthase (dicyclohexylammonium sulfate). The normalizing capacity of dimethylformamide was not compromised by cotreatment with putrescine or spermidine. Both difluoromethylornithine and dicyclohexylammonium sulfate inhibited the growth of monolayer AKR-2B and AKR-MCA. In view of the well documented cytostatic effects of polyamine inhibitors, it is suggested that a decrease in growth by these agents triggers a more normal phenotype in AKR-MCA cells.

Animals↗

PubMed1981

[Synthesis of defined peptide derivatives via aminolysis of 3-[N alpha-acylpepidyloxy)-2-hydroxy-N-alkylbenzamides at elevated temperatures, I. Synthesis of the model peptide derivative Z-Ala-Phe-Gly-N(Et)2 (author's transl)].

Reacting 3-(N alpha-Benzyloxycarbonylalanyl-phenylalanyloxy)-2-hydroxy-N-methylbenzamide with glycinediethylamide at temperatures within 60-100 degrees C, utilizing either dimethylsulfoxide, dimethylformamide or N-methylpyrrolidone as solvents, yielded the corresponding tripeptide derivative Z-Ala-D/L-Phe-Gly-N(Et)2. Depending on the reaction temperature and the nature of the solvent, the isolated tripeptide derivatives contained 0.55% (60 degrees C, dimethylformamide) to 2.5% (100 degrees C, dimethylformamide) of the D-epimer, which could be separated by high-performance liquid chromatography. 3-(N alpha-Benzyloxycarbonylpeptidyloxy)-2-hydroxy-N-methylbenzamide derivatives allow peptide couplings at elevated temperatures even in those cases where the poor solubility of the amino components prevents the condensation step with those methods operating at low temperatures.

Benzamides↗

PubMed1984

Induction of microvillar hydrolase activities by cell density and exogenous differentiation inducers in an established kidney epithelial cell line (LLC-PK1).

Several hydrolase activities characteristic of the apical brush border membrane of renal proximal tubule, leucine aminopeptidase, gamma-glutamyl transpeptidase, alkaline phosphatase, maltase, and trehalase, were identified in cultures of the LLC-PK1 kidney epithelial cell line. A coordinate increase in activities of these enzymes was observed upon development of a confluent cell density and functional membrane polarization. Further large progressive increases in individual hydrolase activities were induced after the addition of compounds known as differentiation inducers. Hexamethylene bisacetamide preferentially induced increased trehalase and maltase activities. Induced trehalase activity exhibited an increased Vmax but a similar Km compared with activity in control extracts. Induction required protein synthesis and was dependent on inducer concentration and exposure time. Treatment of confluent cultures with N,N'-dimethylformamide triggered an induction of maltase, trehalase, alkaline phosphatase, and gamma-glutamyl transpeptidase activities, whereas dimethylsulfoxide induced trehalase and gamma-glutamyl transpeptidase activities. Increased leucine aminopeptidase and maltase activities were observed after addition of the phosphodiesterase inhibitor 1-methyl-3-isobutylxanthine. Induction of trehalase activity by N,N'-dimethylformamide was reversible over a 4-day period after removal of inducer, but effects of hexamethylene bisacetamide were irreversible. These results suggest that the LLC-PK1 cell line reproducibly develops differentiation-specific characteristics under defined conditions in cell culture, which can be individually modulated by chemicals known as inducers of cell differentiation.

Acetamides↗

PubMed2002

Solid phases of tenoxicam.

In this report we describe the preparation and characterization of four polymorphic forms of tenoxicam; they are, three 1:1 stoichiometric solvates with acetonitrile, dioxane, and N,N-dimethylformamide, and an amorphous phase obtained by recrystallization in various solvents. Polymorph IV and solvates with dioxane and N,N-dimethylformamide are reported for the first time in this paper. In addition, three solvates were crystallized in acetone, ethyl acetate, and isopropyl alcohol. These solid forms were characterized by X-ray powder diffraction, differential scanning calorimetry, infrared spectroscopy, thermogravimetry, optical microscopy, and elemental analysis. Solid-state properties, intrinsic dissolution rate, and dissolution kinetics from formulated tablets are also provided.

1-Butanol↗

PubMed1997

A fluorescamine assay for membrane protein and peptide samples with non-amino-containing lipids.

A method is described for determining the concentration of membrane proteins and peptides in the presence of non-amino-containing lipids. The assay is quantitative when used for purified proteins and peptides of known sequence and qualitative when sequences are unknown or samples contain contaminating proteins. In this method, proteins and peptides are hydrolyzed to amino acids followed by derivatization by fluorescamine and spectroscopic detection in a mixed solvent system. A liquid-phase acid hydrolysis separates lipid from the sample and increases the sensitivity and accuracy of the assay. The aqueous-organic solvent, composed of 40% dimethylformamide, has two advantages. First, it suppresses differences in fluorescence between samples with and without residual hydrolyzed lipid, allowing direct comparison of samples and standards regardless of lipid content. Second, the solvent enhances the fluorescence of amino acid derivatives. While the fluorescence intensities of fluorescamine derivatives reach a maximum at approximately 40% dimethylformamide, the emission maximum wavelengths continue to blue-shift at higher concentrations of organic solvent. The selection of an acid hydrolysis mixture based on the fluorescence quenching by different acid mixtures is also reported.

Amino Acids↗

PubMed1978

Influence of antimicrobial agents on contamination and chlortetracycline production.

The possibility of shortening the thermal sterilization time for cultivating media was demonstrated in chlortetracycline fermentation with an industrial strain of Streptomyces aureofaciens. The medium was artificially contaminated with a mixture of eight strains of G+ and G- bacteria isolated from contaminated industrial fermentors, and the following chemical agents, either alone or in combination, were added: formaldehyde, phenol. dimethylformamide, p-aminosalicylic acid and nitrofurazone. Dimethylformamide was inhibitory even at 0.08%. formaldehyde concentrations higher than 0.05%, Nitrofurazone stimulated chlortetracycline production. The best combination was 0.01% formaldehyde added before, and 2.10-3% nitrofurazone added after short sterilization at 120 degrees C.

Aminosalicylic Acid↗

PubMed1992

Sensitivity of nuclear c-myc levels and induction to differentiation-inducing agents in human colon tumor cell lines.

Six human colon tumor cell lines were analyzed for their constitutive levels of the c-myc protein. The nuclear proto-oncogene, c-myc, was detected as an expressed product in all of the human colon tumor cell lines analyzed. The poorly differentiated cell lines HCT116, RKO and C showed c-myc levels that averaged 2-fold greater than their well-differentiated counterparts, i.e., GEO, CBS and FET. When c-myc levels and responses to serum induction were analyzed in the presence of inducers of differentiation, i.e., dimethylformamide, retinoic acid, sodium butyrate and TGF-beta, distinct patterns of sensitivity and resistance emerged. Nuclear c-myc levels were reduced in all the colon cell phenotypes treated with dimethylformamide or sodium butyrate. Only the well-differentiated human colon tumor cell lines were responsive to transforming growth factor-beta. Only one of the human colon tumor cell lines (GEO) responded to retinoic acid. Increased levels of c-myc protein were found to correlate well with greater growth rates and with poor differentiation class. Similarly, a parallel sensitivity to down-regulation of c-myc levels and attenuation of c-myc induction curves for inducers of differentiation were observed in growth sensitive human colon tumor cell lines.

Butyrates↗

PubMed2006

Spectral properties of new N,N'-bis-alkyl-1,4,6,8-naphthalenediimide complexes.

The photophysical properties of two N,N'-bis-alkyl-1,4,6,8-naphthalenediimide (DCN1 and DCN2) have been studied in chloroform and N,N-dimethylformamide solvents. The ability of DCN2 in N,N-dimethylformamide to detect metal cations have been monitored by the fluorescence emission spectroscopy. It has been shown that the fluorescent intensity is very sensitive to the concentration of Fe3+ cations. The reaction of iodine with N,N'-bis-alkyl-1,4,6,8-naphthalenediimide in chloroform solution have been investigated by spectrophotometric method. The results indicate the formation of two CT-complexes [(DCN1)I]+.I3- and [(DCN2)I]+.I3- at donor:acceptor molar ratio of 1:2. The [(DCN1)I]+.I3- shows the characteristic absorptions of I3- ion at 290 and 360 nm while the charge-transfer transition of [(DCN2)I]+.I3- occurs at 310 nm. Three characteristic bands at the far infrared region in each iodine complex are observed around 135, 105 and 85 cm-1 due to nuas (I-I), nus (I-I) and delta (I3-), respectively with C2v symmetry. The values of the complex formation constant, K, and the absorptivity, epsilon have been calculated.

Alkanes↗

PubMed1998

Fractionation of wheat gliadins by counter-current distribution using an organic two-phase system.

A liquid liquid two-phase system based on N,N-dimethylformamide and the two polymers, poly(ethyleneglycol) and Ficoll, useful for partitioning of hydrophobic proteins, has been developed. The system has been applied to a counter-current distribution process in 56 steps for analysing the heterogeneity of proteins extracted with N,N-dimethylformamide from wheat flour. The counter-current distribution patterns of proteins, extracted from eight kinds of wheat, have been analysed. The minimum number of hypothetical proteins necessary to describe the patterns was found to be seven. The relative amount of these hypothetical components varied among the wheats.

Chemical Fractionation↗

PubMed2000

Artefact formation in the determination of residual solvents according to a method of the European Pharmacopeia.

Method 2 of the procedure for the identification and assay of residual solvents, of the European Pharmacopeia 3rd edition 1999 addendum, leads to artefactual formation of N-chlorodimethylamine when the hydrochlorides of basic compounds are examined. This is due to degradation of the dissolution solvent N,N-dimethylformamide under the prescribed conditions. N-Chlorodimethylamine has been detected during analysis of several hydrochloride salts of nitrogen bases including drug substances. Artefact formation did not occur consistently with all the compounds examined, but with diltiazem hydrochloride it was observed in the majority of experiments. The discovery that the alkylating reagent N,N-dimethylaminoethyl chloride (DMC) used in the synthesis of diltiazem gives apparently high yields of N-chlorodimethylamine was cause for concern. However, it has been confirmed that production batches of diltiazem hydrochloride contain <1 ppm of this synthetic intermediate. The formation of N-chlorodimethylamine in the presence of the drug substance is probably due to a reaction between dimethylformamide and HCl, that would be released as a result of hydrolysis by residual water of the O-acetyl function of diltiazem. In view of these findings, the compendial general method should be reviewed. It may be necessary to adopt a different approach to the drafting of methods for volatile impurities, since most of the operating conditions are in practice specific to the substance being examined.

Calcium Channel Blockers↗