Elemental impurities in pharmaceuticals according to ICH-Q3D and Ph. Eur. 5.20

The ICP-MS technique provides information on the concentrations of metals in a sample. The measurement includes the following elements: Na, Mg, K, Ca, Li, Be, B, Al, Si, P, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, As, Se, Rb, Sr, Zr, Nb, Mo, Ag, Cd, In, Sn, Sb, Te, Cs, Ba, Hf, Hg, Tl, Pb, Bi, U. In the results, the elemental concentrations are expressed in units mg/kg.

Determination of the concentrations of Co, Si, P, S, B, and Na in solid chemicals. This method is meant for chemicals like Co(NO3)2. The results include the concentration of the main component (Co) and the concentrations of selected impurities.

Diesel exhaust fluid (DEF) is an additive used in diesel-powered vehicles to help the catalytic reduction of nitrous oxides. Thus, the use of AdBlue and other exhaustive fluids improves ambient air quality. DEF testing package according to ISO 22241:2019 includes the measurements listed below: Urea content (ISO 22241-2C), Density at 20 °C (EN ISO 12185) , Refractive index at 20 °C (ISO 22241-2C), Alkalinity as NH₃ (ISO 22241-2D), Biuret (ISO 22241-2E), Aldehydes (ISO 22241-2F), Insoluble matter (ISO 22241-2G), Phosphate (ISO 22241-2H), Determination of Al, Ca, Cr, Cu, Fe, K, Mg, Na, Ni, and Zn content (ISO 22241-2I).

Spark-OES is a commonly used method to determine the elemental composition of metals and alloys. The method provides a better alternative to other similar analysis techniques (ICP-OES, ICP-MS, XRF) due to its speed and low detection limits. All metallic elements and some non-metallic elements, such as C, N, and S, can be detected in the ppm range. The method is suitable for solid metal pieces with a minimum size of 1 x 1 cm. Sample preparation is included in the analysis.

Determination of total organic carbon (TOC) content of water samples. The results of the analysis will be reported in mg/l.

UPLC-MS/MS analysis for determining the melatonin content in dietary supplements. According to Regulation (EU) No 432/2012, melatonin supplements may be marketed with the following health claims: "Melatonin contributes to the alleviation of subjective feelings of jet lag." The claim can be used if the product contains at least 0.5 mg of melatonin per portion., "Melatonin contributes to the reduction of time taken to fall asleep." The claim can be used if the product contains at least 1 mg of melatonin per portion..

We have various testing services available for ultrapure water. Pricing depends on the selected parameters and the number of samples. Please contact Measurlabs to get an offer. Note that we will provide suitable shipping containers based on the analyses that are ordered. Trace elements by ICP-MS For the determination of elemental impurities, we offer a basic 36-element and an extended 67-element package. The basic package includes the following 36 elements: Li, Be, B, Na, Mg, Al, K, Ca, Ti, V, Cr, Mn, Fe, Co, Ni, Cu, Zn, Ga, Ge, As, Sr, Zr, Nb, Mo, Ag, Cd, Sn, Sb, Ba, Ta, W, Pt, Au, Tl, Pb, and Bi. The extended analysis includes the following elements in addition to the basic package: Ce, Cs, Dy, Er, Eu, Gd, Hf, Ho, In, Ir, La, Lu, Hg, Nd, Os, Pd, Pr, Re, Rh, Rb, Ru, Sm, Sc, Se, Te, Tb, Th, Tm, U, Yb, and Y. Reporting limits depend on the element and specific sample matrix, but typically vary between 0.001 ppb and 0.6 ppb. For this analysis, samples must be delivered in Teflon containers. Hardness Hardness value can be calculated based on the ICP-MS results. Silicon and silica (Si, SiO2) Our service catalog includes the determination of total, dissolved, and colloidal silica (SiO2). Total silicon is analyzed using the ICP-OES technique, and dissolved silicon by UV-VIS (molybdenum heteropoly blue method). Colloidal silica is calculated as the difference between total silica and dissolved silica. Total organic and inorganic carbon (TOC and TIC) We offer TOC determination for ultrapure water samples with a 5 ppb quantification limit. For this analysis, samples must be delivered in certified 40 ml TOC vials. Total inorganic carbon (TIC) analysis can also be performed using a TOC analyzer. Anions by ion chromatography (IC) For anions, we have a basic package and a separate package for organic anions. The basic package includes the following anions: bromide(Br⁻), chloride (Cl⁻), fluoride (F⁻), nitrate (NO₃⁻), nitrite (NO₂⁻), phosphate (PO₄³⁻), and sulfate (SO₄²⁻). Analysis of organic anions includes: acetate, formate, glycolate, propionate, and butyrate. Reporting limits depend on the anion and sample matrix, but typically vary between 0.02 and 1 ppb for basic anions and are around 25 ppb for organic anions. For this analysis, samples must be delivered in HDPE bottles. Cations by ion chromatography (IC) The analysis package for cations includes the determination of the following cations: ammonium (NH4+), calcium (Ca2+), lithium (Li+), magnesium (Mg2+), potassium (K+), and sodium (Na+). Reporting limits typically vary between 2 ppb and 5 ppb. Samples must be delivered in HDPE bottles. PFAS compounds (24 compounds) Analysis includes PFOS, PFOA, PFNA, PFHxS, and 20 other selected PFAS compounds. The complete list of compounds can be provided upon request. The reporting limit is typically 1 ng/L. The sample must be delivered in a plastic PFAS-free bottle, preferably made from HDPE.

Rutherford Backscattering Spectrometry (RBS) can be used to measure the composition of solid samples quantitatively at the surface as well as depth profiling. RBS is used for the analysis of heavy elements and can be combined with ToF-ERDA when lighter elements also need to be analyzed. Elements with similar mass can be difficult to differentiate.

Migration of lead and cadmium from ceramics, glass, and enameled articles. For ceramic articles and tableware, limits defined in Commission Directive 2005/31/EC (amending Council Directive 84/500/EEC) apply: Category Limit for lead Limit for cadmium Articles which cannot be filled and articles which can be filled, the internal depth of which, measured from the lowest point to the horizontal plane passing through the upper rim, does not exceed 25 mm 0.8 mg/dm2 0.07 mg/dm2 All other articles which can be filled 4.0 mg/l 0.3 mg/l Cooking ware; packaging and storage vessels having a capacity of more than three liters 1.5 mg/l 0.1 mg/l In addition, limits for the release of lead (2 mg/article) and cadmium (0.2 mg/article) for articles with a lip and rim area (such as cups and mugs) have been defined in standard ISO 4531-1/2:1998. For glass and enameled products, no harmonized regulation exists currently within the European Union. By convention, limits defined by Commission Directive 2005/31/EC can be applied. However, member states can impose additional or separate restrictions regarding migration limits, tested elements, and/or test conditions. Examples of specific requirements defined at the national level are listed below: Member state Regulation Specific requirements* France Fiche MCDA n°2 (V01 – 01/05/2016) Ceramics & glass: separate migration limits for articles with a lip and rim area, migration limits for Al, Co, and As. Enameled and decorated articles other than ceramics: migration limit for Cr VI. Italy Ministerial Decree of 21/03/1975, as amended Lead glass: separate test method and migration limit for Pb. The Netherlands Commodities Act (Packagings and Consumer Articles) Glass and glass ceramics: separate migration limits for Sb, As, Ba, B, Cd, Ce, Cr, F, Co, Li, Pb, Mn, Ni, Rb, Zr. Ceramics and enamels: separate migration limits for As, Ba, B, Cd, Cr, Co, Hg, Li, Pb, Rb, Se, Sr. Finland Degree (KTM) 268/1992 Glass, enamels, and ceramics with lip and rim area and/or intended for toddlers: separate migration limits for Pb, Cd, Ni, Cr. * Testing for specific requirements is possible for an additional cost Some of the available test methods are listed below: Material type Product type Migration method Available methods Ceramics Flatware (e.g. plates) Total immersion EN 1388-1, ASTM C 738 Ceramics Holloware (e.g. cups) Article fill EN 1388-1, ASTM C 738 Glass Flatware (e.g. plates) Total immersion EN 1388-2 Glass Holloware (e.g. cups) Article fill ISO 7086-1 Ceramics, glass, enameled metal Holloware (e.g. cups) Lip and rim test ASTM C 927

This metal screening analysis includes the semi-quantitative determination of 70 elements. The method can be used, for example, to determine the background concentrations of metals in environmental samples or to study the elemental distribution of unknown samples. Screening is also often performed to assess which metals should be analyzed by a quantitative method. The measurement is performed using a high-resolution ICP-MS technique (ICP-SFMS), which can identify very low elemental concentrations. A semi-quantitative determination of the following elements is included: Ag, Al, As, Au, B, Ba, Be, Bi, Br, Ca, Cd, Ce, Co, Cr, Cs, Cu, Dy, Er, Eu, Fe, Ga, Gd, Ge, Hf, Hg, Ho, I, Ir, K, La, Lu, Mg, Mn, Mo, Na, Nb, Nd, Ni, Os, P, Pb, Pd, Pr, Pt, Rb, Re, Rh, Ru, S, Sb, Sc, Se, Si, Sm, Sn, Sr, Ta, Tb, Te, Th, Ti, Tl, Tm, U, V, W, Y, Yb, Zn and Zr. However, please note that some elements may not be determinable due to matrix interference. During this semi-quantitative analysis, the instrument is calibrated for about 30 elements. The rest of the analytes are quantified using sensitivity factors for calibrated elements with similar mass and first ionization potential, considering isotope abundances. Quantitative analysis is also available at an additional price. During this analysis, all elements are calibrated (excluding halogens and Os). Please ask for an offer for this service.