Elimination of metformin-croscarmellose sodium interaction by competition.

During analytical method development and validation, a strong charge interaction between metformin and croscarmellose sodium was observed when the aqueous solution containing metformin was spiked with croscarmellose sodium. The charge interaction resulted in the retention of metformin in croscarmellose sodium and caused a serious drug recovery problem. The percent recovery of metformin in the solution was much lower than its theoretical values, especially in the low metformin concentration range. To overcome the metformin-croscarmellose interaction, arginine was selected as a competitor for the binding sites on croscarmellose sodium. Because of the competition and stronger interaction between arginine and croscarmellose sodium than metformin and croscarmellose sodium, a complete recovery of metformin in presence of arginine in both low and high concentration ranges was achieved. The effect of arginine on the recovery of metformin and the competition mechanism are discussed in this paper.

Reversed-phase high-performance liquid chromatography behavior of chaotropic counteranions.

The retention behavior of inorganic liophilic anions in reversed-phase HPLC columns was studied. Usually, the addition of these ions to the mobile phase influences the retention of protonated basic analytes similar to the effect of amphiphilic ions (ion-pairing agents). The nature of this influence is the subject of this paper. HPLC retention of perchlorate (ClO4-), tetrafluoroborate (BF4-), and hexafluorophosphate (PF6-) ions was studied on six columns with different bonded phases including alkyl, phenyl and perfluorophenyl phases. The effect of the mobile phase ionic strength on the retention of liophilic ions was investigated. The influence of the type of organic modifier, acetonitrile and methanol, on the retention of inorganic ions was also studied and interpreted on the basis of adsorption from solutions. Semi-empirical expression is suggested for the description of the retention profile of studied liophilic ions versus the eluent composition. Significant retention of these ions is observed in acetonitrile-water eluents. Multilayer-type adsorption of the acetonitrile on the reversed-phase surface and its strong dispersive (or pi-pi) interactions with liophilic ions are responsible for significant retention of these ions. This accumulation of liophilic ions in the adsorbed layer on the surface of reversed-phase material introduces an electrostatic component in the retention of protonated basic analytes.

Separation of ritalin racemate and its by-product racemates by capillary electrophoresis.

Ritalin, [(+)-threo]methylphenidate hydrochloride, is a chiral drug substance with two chiral centers. The drug substance may contain three pairs of enantiomers, [(+)-threo], [(-)-threo], [(+)-erythro] and [(-)-erythro] isomers, and its degradation products, threoritalinic acid racemate. Determination of the optical purity of ritalin drug substance and the amount of its by-product isomers is a critical step in the single-isomer drug development. In order to efficiently recognize the three pairs of enantiomers by one method, capillary electrophoresis (CE) was employed for the separation. The three pairs of enantiomers in CE showed different enantioselectivities with eight different types of CDs. Only 2,6-di-o-methyl-beta-cyclodextrin (DM-beta-CD) and carboxymethyl-beta-cyclodextrin (CM-beta-CD) showed enantioselectivity to all these pairs of enantiomers. With respect to separation resolution and efficiency, DM-beta-CD was chosen as the chiral selector. For optimization of the separation conditions, the concentration of DM-beta-CD, pH of the buffer solution, and temperature of the capillary were further studied.

Enhancement of chiral recognition by formation of a sandwiched complex in capillary electrophoresis.

For chiral primary amino compounds not separable by cyclodextrins alone, chiral recognition was successfully achieved by the formation of a sandwiched complex of the non-chiral 18-crown-6, the chiral amine and cyclodextrin (CD) [18-crown-6+amino compound+CD]. The separation of 1-methyl-3-phenylpropylamine and 1,2,3,4-tetrahydro-1-naphthylamine racemates showed the special function of the non-chiral 18-crown-6 on chiral recognition. By formation of the sandwiched complex, the chiral center of 1-methyl-3-phenylpropylamine was successfully recognized, and resolution of 1,2,3,4-tetrahydro-1-naphthylamine dramatically increased. In these studies, the mobility differences of the enantiomers were evaluated as a function of the concentration of cyclodextrins with and without the 18-crown-6, and as a function of the concentration of the 18-crown-6. In addition, the separations by this method were compared to those by the chiral 18-crown-6 reagent.

Effect of skin pigmentation on pulse oximetry accuracy in the emergency department.

OBJECTIVE: To determine whether pulse oximeter (PO) accuracy and signal quality are affected by level of skin pigmentation. METHODS: Observational study in a community hospital ED. Consecutive adult patients undergoing arterial blood gas determination were enrolled into the study. Skin pigmentation was determined by comparison with standardized color swatches under controlled lighting; assigned values were used to stratify patients into 3 groups (light, intermediate, and dark) using predetermined criteria. Simultaneous with arterial blood sampling, staff recorded PO reading of O2 saturation using the Nellcor D-25 oximeter. PO values were compared with criterion standard values measured using a 4-wavelength spectrophotometer or co-oximeter. PO signal quality also was recorded. Bias (the mean difference between PO and co-oximeter-measured values of hemoglobin saturation) and precision (the standard deviation of the bias) were calculated. Groups were compared using one-way ANOVA, Bartlett's test for variances, and chi2 test. RESULTS: O2 saturation data were obtained for 284 patients. Bias values did not differ between the 3 skin pigment groups (p = 0.79). Precision was of borderline significance (p = 0.05), but there was no dose-response relation between skin pigmentation and precision. Study personnel reported suboptimal PO function most often among patients in the dark group (p = 0.003), but this finding was of no clinical significance. PO signal failure was rare (<1% of all patients). CONCLUSIONS: Although several prior studies suggest the contrary, this study found that skin pigmentation does not affect the bias or precision of pulse oximetry. Furthermore, skin pigmentation has no clinically significant effect on PO signal quality.

Chiral separation of primary amino compounds using a non-chiral crown ether with beta-cyclodextrin by capillary electrophoresis.

A non-chiral crown ether (18-crown-6) along with beta-cyclodextrin (beta-CD) was used to achieve enantioselective separations of primary amino compounds in capillary electrophoresis. In this new method, the amino group of these compounds is protonated in a low pH separation buffer and forms a selective host-guest complex with the crown ether (amino compound+18-crown-6). The hydrophobic portion of the host-guest complex is then incorporated into the cavity of the beta-cyclodextrin. The amino compound is sandwiched between the crown ether and the cyclodextrin (18-crown-6+amino compound+beta-CD) and thus determines or enhances the enantioselective recognition. It is postulated that the formation of this sandwich results in a more selective chiral interaction between the molecule and beta-cyclodextrin. The chiral recognition is dependent upon the formation of this sandwich complex. This method has been used to achieve enantioselectivity of primary amino compounds with a wide variety of substitutions.