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This study details the isolation, identification, and characterization of ambroxol's unknown impurity. One unknown impurity of ambroxol was formed in the formulated drug under stress conditions [40°C /75% relative humidity (RH) for 6 months] with the relative retention time (RRT) 0.68 in RP-HPLC. The impurity was enriched by exposing it to heat and it was isolated by using preparative HPLC. The enriched impurity was purified and characterized using the following sophisticated techniques: 2D NMR (gDQ-COSY, gHSQC, and gHMBC), FTIR, and LC-MS/MS. On the basis of the spectral data, the impurity was characterized as trans-4-(6,8-dibromoquinazolin-3(4H)-yl)cyclohexanol.

Statistical experimental design was used to optimize the chromatographic separations of two pharmaceutical compounds from their respective potential impurities. A fractional factorial design was utilized to study the effects of pH, organic solvent in mobile phases A&amp, B, and flow rate on the resolution of Rabeprazole and Rabeprazole Sulfone, which had closely eluting peaks. A desirability function applied to the optimized conditions predicted the peak resolution between 2.2 and 2.7 for the Rabeprazole &amp, Rabeprazole Sulfone impurity. The chromatographic method employed an Acquity UPLC, BEH C18 column (100 x 2.1 mm i.d., 1.7 μm particle size) with the mobile phase consisting of a phosphate buffer, pH 6.5, and acetonitrile in a gradient program. The flow rate and injection volumes were 0.45 mL/min &amp, 5 μl, respectively, and detection was done at 254 nm. The chromatographic method was validated for linearity, accuracy, precision, specificity, and ruggedness according to ICH guidelines. The results clearly showed that the quality by design concept could be effectively applied to optimize a UPLC chromatographic method with fewer trials and error-free experimentation.

A sensitive, stability-indicating gradient RP-HPLC method with PDA detection has been developed for the simultaneous analysis of drotaverine impurities in active pharmaceutical ingredient (API) and pharmaceutical formulations. Efficient chromatographic separation was achieved on an XTerra RP18, 150 × 4.6 mm, 5 μm column using gradient elution at 230 nm detection wavelength. The optimized mobile phase consisted of a 0.02 M potassium dihydrogen orthophosphate buffer of pH 3.0 as solvent A and acetonitrile as solvent B. The flow rate of the mobile phase was 1.0 mL min(-1) with a column temperature of 25°C. The method showed linearity over the range of 0.251-10.033 μg/mL, 0.231-9.995 μg/mL, 0.230-10.089 μg/mL, 0.334-10.011 μg/mL, and 0.324-10.050 μg/mL for impurities 1, 2, 3, 4, and drotaverine, respectively, with a correlation coefficient greater than 0.999. The relative retention times and relative response factors of impurities 1, 2, 3, 4 were 0.36, 0.90, 1.42, 1.55 and 1.04, 0.84, 1.10, 1.30, respectively. The drotaverine formulation sample was subjected to the stress conditions of acid, base, oxidative, thermal, humidity, and photolytic degradation. Drotaverine was found to degrade significantly in peroxide, base, and heat stress conditions. The degradation products were well-resolved from drotaverine and its impurities. The peak purity test results confirmed that the drotaverine peak was homogenous and pure in all stress samples and the mass balance was found to be more than 98%, thus proving the stability-indicating power of the method. The developed method was validated according to ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision, and robustness.

The utilization of selected minerals when sugars were supplemented to basal diets was investigated in two separate, laboratory-controlled human feeding studies. Fructose-fed subjects had higher fecal excretions of iron and magnesium than did subjects fed sucrose. Apparent iron, magnesium, calcium, and zinc balances tended to be less positive during the fructose feeding period as compared to balances during the sucrose feeding period. Conversely, high fructose corn syrup (HFCS) did not affect the mineral balances when compared to sucrose feeding. Subjects fed fructose experienced diarrhea which possibly decreased absorption of minerals and thus increased fecal mineral losses. No such adverse effects were noticed when HFCS was fed.

ROSALIEAMOS,3 NANCY BETTS,4 CONSTANCE GEORGIOU,S SHARON HOERR,6 RAO IVATURI,7 AND JANE VOICHICK 2 lDepartment of Nutritional Sciences, Shantz 309, The University of Arizona, Tucson, Arizona 85721; 2Department of Nutritional Sciences, University of Wisconsin-Madison, 1415 Linden Drive, Madison, Wisconsin 53706; 3Department of Family and Consumer Sciences Ed., 220C Mackay Hall, Iowa State University, Ames, Iowa 50011; 4202 Ruth Leverton Hall, University of Nebraska, Lincoln, Nebraska 68583-0806; SNutrition and Food Management, Milam Hall 108, Oregon State University, Corvalis, Oregon 97331-5103; 6Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan 48824-1224; 7Department of Home Economics, Indiana State University, Terre Haute, Indiana 47809