UHPLC-APCI-TQ-MS analytical method to quantify nitrosamine impurities in the commercial formulation of metformin and glipizide

As per the ICH M7 guideline nitrosamine impurities are referred to as cohort of concern which are having a potential significant carcinogenic risk and for the safe human consumption of drug products, the levels of nitrosamine impurities need to be controlled as per respective permissible daily exposures (PDE). An accurate, precise, sensitive, and robust UPLC-APCI-TQ-MS/MS method has been developed for the quantification of eight nitrosamine impurities in the marketed formulation of metformin and glipizide Tablets. Chromatographic separation was achieved using Kinetex® 150 × 3.0 mm Biphenyl 100 Å, 2.6 µm column with mobile phase A (0.1% w/v formic acid dissolved in water) and mobile phase B (0.1% w/v formic acid dissolved in methanol) with a flow rate of 0.4 mL per minute having run time of 20 min with gradient mode of elution. As per ICH Q2(R1) guideline the method had been validated which demonstrates the sensitivity of the developed method with a good linearity range of 1–5 ng/mL for all eight nitrosamine impurities. The validation parameters suggest that the developed method for the simultaneous quantification of eight nitrosamine impurities in the marketed formulation of metformin hydrochloride and glipizide can be routinely applied in the quality control laboratory. </p

Dataset

The dataset file contains the fully de-identified study dataset. The first tab contains important information regarding the dataset. The second tab contains the variable dictionary. The final two tabs contain de-identified study data with variables unlabeled (coded) and labelled

Additional file 1: Table S1. of Variability in monthly serum bicarbonate measures in hemodialysis patients: a cohort study

Baseline characteristics by quartiles of baseline serum bicarbonate. Table S2. Transition matrix showing the number of serum bicarbonate measurements in a clinical category in a given month and in the subsequent month. Figure S1. Predicting next month’s serum bicarbonate level, within tertiles of 90-day mean serum bicarbonate. For a single monthly serum bicarbonate measurement falling within the low (<22 mEq/L), normal (22–26 mEq/L), and high (>26 mEq/L) categories defined by clinical cutpoints, the percentage of measurements in the following month that remain in the same category or change category are shown within tertiles of the mean serum bicarbonate during the first 90 days after admission to the dialysis unit: ≤22 mEq/L (n = 62), 22.25 – 24 mEq/L (n = 65), ≥24.25 mEq/L (n = 54). Percentages may not sum to exactly 100 % due to rounding. Figure S2. Predicting next month’s serum bicarbonate level, within tertiles of variability value. For a single monthly serum bicarbonate measurement falling within the low (<22 mEq/L), normal (22–26 mEq/L), and high (>26 mEq/L) categories defined by clinical cutpoints, the percentage of measurements in the following month that remain in the same category or change category are shown within tertiles of the mean value of VV (Variability Value) for each patient during follow-up: Low (mean VV ≤2.18 mEq/L), Medium (mean VV = 2.19 to 2.75 mEq/L), and High (mean VV ≥2.76 mEq/L). Percentages may not sum to exactly 100 % due to rounding. Table S3. Multivariable-adjusted associations of clinical and laboratory characteristics with serum bicarbonate variability over time within and after the first 6 months. (DOCX 67 kb