Mercury Determination in Certifiable Color Additives Using Thermal Decomposition Amalgamation and Atomic Absorption Spectrometric Analysis

Background Color additives requiring batch certification by the U.S. Food and Drug Administration (FDA) have Code of Federal Regulations (CFR) specification limits for certain elements and are usually analyzed by x-ray fluorescence spectrometry (XRF). However, sensitivity for Hg is too low in some color additives. Objective The thermal decomposition amalgamation-atomic absorption spectrometric (TDA-AAS) technique was investigated for providing quick and accurate determinations of Hg in certifiable color additives. Methods Tests were performed to optimize conditions and test reliability of Hg determinations at and below the CFR specification limit of 1 mg/kg. Results Sensitivity is much improved over XRF with limits of quantitation of 0.03 mg/kg for highly homogeneous color additives. Conclusions The TDA-AAS method can be used for determining Hg concentrations at and below the CFR specification limit. The technique is effective for all color additives, including those that are difficult to analyze by XRF, but less efficient for color additives that quickly deteriorate the catalyst. Regular quality checks using certified reference materials and in-house matrix-matched check standards are essential. Highlights The TDA-AAS method is applicable for use in routine color additive batch certification. Certain matrices (notably those that release nitrogen or sulfur oxides or halogens upon combustion) necessitate more frequent replacement of the catalyst and recalibration, impacting productivity. Color additives containing BaSO4, in color additive lakes, that are difficult to analyze by other techniques are well suited for TDA-AAS analysis.

Determination of Seven Manufacturing Impurities in FD&C Red No. 40 by Ultra-High-Performance Liquid Chromatography

Background: The U.S. Food and Drug Administration batch-certifies color additives to ensure that each lot meets published specifications for coloring food, drugs, and cosmetics. Objective: An ultra-high-performance LC (UHPLC) method was developed to determine seven manufacturing impurities in the monoazo color additive FD&C Red No. 40 (R40). The analytes consist of two intermediates, an impurity originating from one intermediate, a reaction by-product, and three subsidiary colors. The intermediates are 4-amino-5-methoxy-2-methylbenzenesulfonic acid [cresidine-p-sulfonic acid (CSA)] and 6-hydroxy-2-naphthalene sulfonic acid sodium salt (SS). The impurity originating from the intermediate SS is 6,6′-oxybis[2-naphthalenesulfonic acid] disodium salt. The reaction by-product is 4,4′-(diazoamino)bis[5-methoxy-2-methylbenzenesulfonic acid disodium salt. The subsidiary colors are sodium salts of CSA coupled with 2-naphthol-3,6-disulfonic acid, 2-naphthol-6,8-disulfonic acid, or 2-naphthol. Methods: Samples of R40 were dissolved in an ammonium acetate buffer modified to pH 9.2, filtered, and analyzed by UHPLC. Quantitation of the analytes was performed by calibration in the presence of the color additive matrix. Results: UHPLC validation studies showed linear calibration curves (R2 = 0.9999), good recovery (95–121%) and precision (RSDs = 1.0–6.3%), and LOQs ranging from 0.002 to 0.030%. Survey analyses of 31 samples from 11 manufacturers yielded results by the new UHPLC method and a previously used HPLC method that are consistent within experimental error. Conclusions: The new UHPLC method provides faster analysis time, improved separation, and similar sensitivity compared to the HPLC method. Highlights: An UHPLC method was developed and validated to determine seven manufacturing impurities in R40 submitted to the FDA for batch certification.

Strategies for Rapid Risk Assessment of Color Additives Used in Medical Devices

Many polymeric medical devices contain color additives for differentiation or labeling. Although some additives can be toxic under certain conditions, the risk associated with the use of these additives in medical device applications is not well established, and evaluating their impact on device biocompatibility can be expensive and time consuming. Therefore, we have developed a framework to conduct screening-level risk assessments to aid in determining whether generating color additive exposure data and further risk evaluation are necessary. We first derive tolerable intake values that are protective for worst-case exposure to 8 commonly used color additives. Next, we establish a model to predict exposure limited only by the diffusive transport of the additive through the polymer matrix. The model is parameterized using a constitutive model for diffusion coefficient (D) as a function of molecular weight (Mw) of the color additive. After segmenting polymer matrices into 4 distinct categories, upper bounds on D(Mw) were determined based on available data for each category. The upper bounds and exposure predictions were validated independently to provide conservative estimates. Because both components (toxicity and exposure) are conservative, a ratio of tolerable intake to exposure in excess of one indicates acceptable risk. Application of this approach to typical colored polymeric materials used in medical devices suggests that additional color additive risk evaluation could be eliminated in a large percentage (≈90%) of scenarios.