Chiral separation of lobeline analogs using high performance capillary electrophoresis and derivatized cyclodextrins as chiral additives.

High performance capillary electrophoresis (HPCE) methods are described that will separate the enantiomers of various lobeline analogs synthesized in these laboratories. "Cyclodextrin array analysis" was used for preliminary screening and electrophoresis conditions were optimized for each investigated analog. The lobeline analogs under consideration were investigated as potential nicotinic agonists for the treatment of neurodegenerative disorders, such as Alzheimer's disease. Native alpha (alpha)-, beta (beta)-, and gamma (gamma)-cyclodextrins, methyl-beta-cyclodextrin (M-beta-CD), heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DM-beta-CD), and heptakis-(2,3,6-tri-O-methyl)-beta-cyclodextrin (TM-beta-CD), hydroxypropyl-alpha-cyclodextrin (HP-alpha-CD), hydroxypropyl-beta-cyclodextrin (HP-beta-CD) and hydroxypropl-gamma-cyclodextrin (HP-gamma-CD) were used as run buffer additives and their effect on the enantiomeric resolution of the lobeline analogs was investigated. The effect of pH, buffer concentration, voltage, temperature and organic modifier concentration on the enantiomeric resolution of the lobeline analogs was investigated. The most suitable conditions for each compound were chosen and, with detection at a wavelength of 200 nm, optimized.

Solution conformation of model polypeptides with the use of particle beam LC/FT-IR spectrometry and electrospray mass spectrometry.

Solution conformations of the polypeptides beta endorphin (beta-END) and a cysteine peptide (CYSP) were investigated with the use of particle beam LC/FT-IR spectrometry. Gradient elution HPLC with mobile phases that contained acetonitrile with 0.1% TFA (v/v) and 0.1% aqueous TFA (v/v) were used. The conformations of both polypeptides were studied in 0.9% sodium chloride injection USP, 5% dextrose in water injection USP and sterile water for injection USP. Additional conformational studies over a pH range of 2-10, temperatures of 25, 50, 75 and 100 degrees C and after storage for 24 h were investigated. The studies indicated that the two polypeptides did not behave similarly under identical conditions. It was observed that both beta-END and CYSP had slightly different conformations in the various parenteral solutions. It was also shown that the conformation of CYSP changed with both pH and temperature while beta-END was conformationally stable to both temperature and pH. The identity of the peptides and the conformationally sensitive charge-state intensities of the peptides were investigated with electrospray ionization mass spectrometry (ESI/MS). The combination of IR and MS data allowed an estimation of solution effects on the conformations of the model polypeptides.

Solution conformation of model peptides with the use of particle beam LC/FT-IR spectrometry and electrospray mass spectrometry.

Solution conformations of the peptides angiotensin I (Ang I) and POMC-X (an octapeptide fragment of proopiomelanocortin) were investigated with the use of particle beam liquid chromatography/Fourier transform infrared (LC/FT-IR) spectrometry. Gradient elution high-performance liquid chromatography (HPLC) with mobile phases that contain acetonitrile, 2-propanol, 0.1% heptafluorobutyric acid (HFBA) and 0.1% trifluoroacetic acid (TFA) were used. The conformations of both peptides were studied in 0.9% sodium chloride injection USP, 5% dextrose in water injection USP and sterile water for injection USP. Additional conformational studies over a pH range of 2-10, to a temperature of 75 degrees C and after a storage time of 24 h were investigated. The studies indicated that the two peptides do not behave similarly under identical conditions. It was observed that both Ang I and POMC-X had slightly different conformations in the various parenteral solutions. It was also shown that the conformation of Ang I changed with both pH and temperature while POMC-X was conformationally stable to both temperature and pH. The identity of the peptides and the conformationally sensitive charge-state intensities of the peptides were investigated with electrospray ionization mass spectrometry (ESI/MS). The combination of infrared and mass spectrometric data allowed a thorough estimation of solution effects on the conformations of the model peptides.

Stability of ondansetron hydrochloride and 12 medications in plastic syringes.

The stability and compatibility of ondansetron hydrochloride with neostigmine methylsulfate, naloxone hydrochloride, midazolam hydrochloride, fentanyl citrate, alfentanil hydrochloride, atropine sulfate, morphine sulfate, meperidine hydrochloride, propofol, droperidol, metoclopramide monohydrochloride, and glycopyrrolate were studied. Ondansetron 1.33 or 1.0 mg/mL was combined with 0.9% sodium chloride injection and each of the 12 drugs in duplicate in plastic syringes (or glass for propofol). The syringes were stored at 21.8-23.4 or 4 degrees C in the dark, except for those containing propofol, which were stored at ambient temperature. Samples were removed at 0, 4, 8, and 24 hours for analysis by high-performance liquid chromatography and pH measurement; the propofol-containing samples were removed at 0, 1, 2, and 4 hours. Syringes were visually assessed for color and clarity, and particulate content was measured with a particle counter at the end of the study period. All solutions containing ondansetron retained more than 90% of their initial ondansetron concentration. Solutions containing each of the other drugs except droperidol retained more than 90% of their initial concentration of these drugs. The solutions containing droperidol retained more than 90% of their initial droperidol concentration for up to eight hours at ambient temperature but precipitated quickly at 4 degrees C. In combinations of ondansetron 1.33 or 1.0 mg/mL and 10 of 12 drugs, all drugs were stable for 24 hours in plastic syringes at 23 and 4 degrees C; ondansetron hydrochloride 1.0 mg/mL and propofol 1.0 and 5.0 mg/mL in admixtures were stable for 4 hours, and droperidol on its own and combined with ondansetron 1.0 mg/mL was stable for no more than 8 hours at ambient temperature.

Determination of metronidazole in vaginal tissue by high-performance liquid chromatography using solid-phase extraction.

A sensitive high-performance liquid chromatographic (HPLC) method for the determination of metronidazole in vaginal tissue is reported. The method uses a Zorbax SB phenyl column with a 0.01 M aqueous monobasic potassium phosphate buffer (pH 4.0)-absolute methanol (85:15, v/v) as mobile phase at a flow-rate of 1.0 ml/min and detection at 313 nm. Tinidazole was used as the internal standard. The method employed homogenization of tissue followed by solid-phase extraction. The quantitation was achieved within 30 min with sensitivity in the ng/g range. Metronidazole was linear in the 100-2000 ng/g range. The accuracy and precision were in the 1-4% range for the drug and the limit of detection was approximately 100 ng/g based on a signal-to-noise ratio of 3 and a 1009-microliters injection.