Multivitamins are consumed for a wide assortment of reasons such as to compensate for diets or eating habits that limit the intake of essential vitamins and nutrients. The National Center for Health Statistics reported that among U.S. adults aged 20 and over, 57.6% used any dietary supplement in the past 30 days, with multivitamin-minerals being the most commonly used supplement (Mishra et al., 2021). It is estimated that one-third of all adults in the United States, and one-quarter of children and adolescents consume multivitamins.(Cowan et al., 2018; Qato et al., 2018) Additionally, most pregnant women take multivitamins as a source of folic acid, iron, iodine, and vitamin D. (Wong et al., 2019)
Research has shown that several mineral components are beneficial and necessary for the wellbeing of individuals (National Academies, 2019). For example, iron is needed for growth and development, in the production of hemoglobin, and to make essential hormones. However, high levels of iron can cause an upset stomach, constipation, nausea, abdominal pain, vomiting, and fainting (National Institutes of Health, 2021). Trace elements can also impact human health. Chromium, copper, zinc, selenium, iodine, and molybdenum are among the nutritional elements; toxic elements include arsenic, cadmium, lead, and mercury (Mehri, 2020).
Monitoring nutritional and toxic elements in food, cosmetics, and multivitamins is part of the Food and Drug Administration’s (FDA) mission to protect and promote public health. The companies selling these products are responsible to ensure that the labels meet all the requirements, including the accuracy of nutrient declarations. To assist in verifying that the nutrient contents are accurately listed, there is a great interest in methods that ensure that the labels for multivitamins are reflective of the actual contents of the product.
Determination of the elemental composition of foods and multivitamins typically involves acid decomposition followed by analysis using Inductively Coupled Plasma – Mass Spectrometry (ICP-MS) and/or Optical Emission Spectroscopy (ICP-OES) (Canbay & Doğantürk, 2017; Cubadda, 2004; Dolan et al., 2003; Kauffman et al., 2007; Krejčová et al., 2006; Marrero et al., 2013). Additionally, square wave anodic stripping voltammetry, neutron activation analysis, flame graphite furnace atomic absorption spectroscopy, and electrothermal atomic absorption spectrometry, among others, have been reported (Hight et al., 1993; Reis & Saiki, 2009; Soltyk et al., 2003; Turk et al., 2013). Solution-based methods of analysis of multivitamin supplements require decomposition of the materials using perchloric, hydrofluoric, hydrochloric, and/or nitric acid followed by dilution of the samples. Such methods invariably involve extensive sample preparation, handling of toxic substances, and are time consuming and labor intensive. A review article published in 2011 describes the use of atomic spectroscopy in the pharmaceutical industry (Lewen, 2011).
Direct analysis of solids by Laser Ablation–Inductively Coupled Plasma–Mass Spectrometry (LA-ICP-MS) is widely accepted and constitutes a powerful analytical tool for numerous types of materials (Becker, 2002; Gunther & Hattendorf, 2005; Koch & Gunther, 2011; Limbeck et al., 2015; Russo et al., 2002). Some benefits of LA-ICP-MS for food and supplement analysis include a smaller amount of sample required, fast sample exchange and high throughput, minimal carryover in comparison with liquid sample introduction, reduction of contamination and analyte loss that would otherwise occur during acid digestion, and minimal sample preparation requirements (Russo et al., 2002). One drawback of solid analysis by LA-ICP-MS is elemental fractionation, where the isotope or elemental ratio detected may not be entirely representative of the composition of the original sample (Limbeck et al., 2015). In terms of ablation behavior, elements fall into several distinct clusters in which they correlate well with each other during the ablation period; therefore, an element from the same cluster can be used as an internal reference for the rest of the elements in the same group, thus mitigating the quantitative discrepancies that result from fractionation (Longerich et al., 1996). A second drawback of LA-ICP-MS is the dissimilarity in the interaction between the laser beam and the sample surface observed with different matrices. This effect causes changes in the ablated mass in relation to the properties of the matrices in question (Kroslakova & Günther, 2007). A promising approach for quantification is the preparation of matrix-matched calibration standards using materials with the same matrix composition as the samples (Fitzpatrick et al., 2008; Miliszkiewicz et al., 2015; Perkins et al., 1991; Shaheen & Fryer, 2011; Sinclair et al., 1998; Vanheuzen & Morsink, 1991; Zhu et al., 2013).
Analytical methods of pharmaceuticals and multivitamin supplements by LA-ICP-MS is limited, especially studies in which solution and laser ablation ICP-MS complementary results are reported. The scarcity of laser ablation studies is mostly due to the lack of reference materials and matrix-matched calibration standards; only a few studies are available (Augusto et al., 2017; Bu et al., 2013; Lam & Salin, 2004; Rudovica et al., 2014). Augusto et al. described the use of cellulose as a binder for creating pellets followed by LA-ICP-MS determination of nutrients and contaminants in food and supplements (Augusto et al., 2017). Bu et al. reported the analysis of six herbal products by LA and solution-based ICP-MS using the National Institute of Standards and Technology (NIST) Standard Reference Material (SRM®) 1573a (tomato leaf) as a one-point calibrant (Bu et al., 2013). Lam and Salin described the analysis of pharmaceutical tablets (10% and 20% Neusilin) by LA-ICP-MS and Laser Ablation–Inductively Coupled Plasma–Atomic Emission Spectroscopy (LA-ICP-AES) using a three point calibration made of Neusilin at different concentrations (Lam & Salin, 2004). Rudovika et al. reported the LA-ICP-MS analysis of elemental impurities in an active pharmaceutical ingredient using laboratory-made matrix calibration standards for quantification by adding inorganic salts at certain concentrations to the main pharmaceutical ingredient (Rudovica et al., 2014).
In this work, the development and optimization of an analytical method based on LA-ICP-MS that can be applied specifically to multivitamins is presented. The technique offers quick and automated sample analysis without the use of corrosive acids and extensive sample preparation. This method is especially useful for products such as multivitamin tablets which are resistant to nitric acid digestion and require the use of hydrofluoric and/or perchloric acids. The developed method aims to reduce the effects of fractionation and differences in ablation yields between different materials by creating a matrix-matched calibration and by normalization to an internal standard added to the samples.