Direct high-performance liquid chromatographic separation of the enantiomers of venlafaxine and 11 analogs using amylose-derived chiral stationary phases.

A direct liquid chromatographic enantioselective separation of venlafaxine and 11 analogs was obtained in the normal phase mode using Chiralpak AD. For some compounds, a comparison between the enantioseparation using coated and immobilized amylose tris(3,5-dimethylphenylcarbamate) chiral stationary phases (Chiralpak AD and Chiralpak IA, respectively) was made. The best separations were achieved on Chiralpak AD with ethanol as alcoholic modifier in a mobile phase made basic by DEA addition: separation factor ranges between 2.08 and 1.15 and resolution factor between 7.0 and 1.0. Using the same CSP and 2-propanol doped with TFA as acidic modifier, 10 compounds were enantioseparated with separation factor ranging between 1.40 and 1.04 and resolution factor between 3.1 and 0.3. The use of ethanol as alcoholic modifier also has the advantage of better solubility of the compounds in the mobile phase. The nature of the substituent (electron donating or withdrawing) affects in general the separation factor. A memory effect that involves a long equilibration time of the CSP is present when switching from an acidic mobile phase to a basic one.

Direct high-performance liquid chromatographic separation of the enantiomers of an aromatic amine and four aminoalcohols using polysaccharide chiral stationary phases and acidic additive.

The HPLC enantiomeric separation of N-benzyl-alpha-methyl-benzylamine, phenylalaninol, tryptophanol, 2 (diphenylhydroxymethyl)pyrrolidine, and isoproterenol was accomplished in the normal-phase mode using two polysaccharide-derived chiral stationary phases (CSPs) and various n-hexane/2-propanol mobile phases with acidic (TFA) or basic (DEA) additive. The compounds were separated without any derivatization and separation factor range between 2.09 and 1.09 with resolution factor 3.4 and 0.4, respectively. The best separation of the enantiomers of the amine was achieved on amylose tris (3, 5-dimethylphenylcarbamate) CSP with TFA additive in the mobile phase; in acidic conditions, instead, the best enantioseparation of the aminoalcohols was achieved on cellulose tris (3, 5-dimethylphenilcarbamate). A long equilibration time of the CSP when switching from an undoped mobile phase to a doped one is required to obtain reproducible results.

Racemization at C-2 of naringin in sour oranges with increasing maturity determined by chiral high-performance liquid chromatography.

Naringin is the major flavanone-7-O-glycoside of sour orange, and it is mainly responsible for the bitter taste of the fruit. The relative content of (2S)- and (2R)-naringin in the albedo of sour oranges during maturation in the entire season was determined by normal phase HPLC using Chiralcel OD-H as chiral stationary phase and n-hexane/ethanol doped with 0.5% of TFA as mobile phase. HPLC traces were complicated by the presence of (2S)-neohesperidin, and a software-guided analysis was developed to assess the relative amount of the C-2 diastereomers of naringin. A sigmoid curve was obtained showing variation from 94% of (2S)-naringin in very immature fruits to 69.7% in mature fruit samples. Spontaneous epimerization of (2S)-naringin in the ethanolic solutions of the albedo was noted after prolonged keeping for less acid samples. The separation of the C-2 diastereomers of other flavanoid-7-O-glycosides present in Citrus (neoeriocitrin, neohesperidin, and eriocitrin) was also obtained by chiral HPLC and afforded the identification, including stereochemistry, of the eluting peaks in the HPLC traces of the albedo extracts.

Chiral high-performance liquid chromatographic separation and circular dichroism spectra of the enantiomers of cytotoxic aristocularine alkaloids.

The HPLC enantiomeric separation of the racemic cularinoid alkaloids N-p-methoxy-1,alpha-dihydroaristoyagonine (1) and 4',5'-demethoxy-1,alpha-dihydroaristoyagonine (2) was accomplished using five chiral stationary phases (CSPs), some of them polysaccharide-derived ones. The molecular size and conjugative effect strongly affect the different enantioselectivity of the compounds 1 and 2 on the various CSPs investigated. Single enantiomers of 1 were isolated by repeated injections on an analytical HPLC column, and their circular dichroism spectra and optical rotations were measured. The cytotoxicity of the isolated enantiomers was measured on a human colon carcinoma cell line and compared with that of the racemic compound.

Intraoperative examination of sentinel nodes in breast cancer: is the glass half full or half empty?

BACKGROUND: Intraoperative identification of positive sentinel lymph nodes in patients with breast cancer may avoid a return to the operating room. METHODS: In a group of 402 consecutive patients with primary breast cancer who underwent sentinel lymph node biopsy, an intraoperative examination (IE) was obtained in 236 cases either by frozen section (FS; n = 68) or by touch preparation cytology (TP; n = 168). RESULTS: IE had an accuracy of 89% (209 of 236), but it identified only 52 of 77 positive cases (sensitivity, 68%). There were 25 false-negative cases (13.7%), of which 7 were macrometastases and 18 by micrometastases (P < .001). Six macrometastases were missed by TP and one by FS (P = .9). There were two false-positive cases (3.7%). Overall, 48 (20%) of 236 patients avoided a delayed return to the operating room for a completion lymphadenectomy because of IE findings. This occurred in 10% of patients with tumors <1 cm in diameter, in 20% of those with tumors between 1 and 2 cm, and in 34% of those with tumors >2 cm in diameter (P = .05). The cost savings for the Italian Health System amounted to 198,040 (US$223,794) in these patients. CONCLUSIONS: IE has acceptable sensitivity for lymph node macrometastases, but it is a weak tool for diagnosing micrometastases. FS and TP are roughly equivalent. IE allows management changes, because approximately 20% of all patients are expected to undergo synchronous axillary dissection, and it is particularly helpful in T2 patients. This may allow substantial cost savings for the health-care system.