Heavy Metals Test

Laser ablation ICP-AES and LA-ICP-MS were also proposed for rapid, direct analysis of tablets containing metallic species.194 Compendial heavy metal tests based on wet chemistry are among the most labor-intensive tasks in pharmaceutical laboratories. Both ICP-MS and ICP-OES have been proposed as alternatives for compendial methods and have the advantages of smaller sample size, element-specific information, quantitation, rapid sample throughput, and significantly improved accuracy.195-198... 

The separation of basic and metal-sensitive compounds is difficult on silica-based stationary phase materials, but these separations can be performed on vinyl alcohol copolymer gels. Examples are the separation of methallothionein from dolphin kidney, a-, j8-, and y-endorphin, and nucleotide and nucleoside mixtures.8 However, an analytical-scale separation may also be performed on surface-modified wide-pore silica gels (pore size 300 A or more), using columns which showed a negative response in the heavy metal test described above. 

Upon obtaining this information a nnmber of heavy metal tests were carried out but the levels were found to be insignificant. Enrther reflection on the problem led to the idea that EDTA is itself a base and the degradation was also known to be enhanced via low pH. Accordingly, experiments were carried out varying the bases used to determine if the cnlprit of the degradation problem was excess acid in the drug substance (Table 3). 

We focus on the requirements for registration in Japan. Thus, we provide information that considers the peculiarities of the requirements for the JP heavy metals test at the method development process. The compendial descriptions and relevant ICH guidelines in relation to this chapter are listed in the reference section. The principles for the validation requirements discussed in this chapter can be applied to heavy metal testing in general. 

Heavy metal testing allows us to detect substances with a low redox potential. If the test compound is sensitive to a number of different oxidants or catalysts, such as hydrogen peroxide, iron (III), and copper (II), it is advisable to consider the substance as potentially very sensitive to oxidation. In this case, it is wise to consider a preformulation involving the use of antioxidants or special protecting conditions. 

Sanchez-Dardon J, Voccia I, Hontela A, Chilmonczyk S, Dunier M, Boermans H, Blakley B, Fournier M. 1999. Immunomodulation by heavy metals tested individually or in mixtures in rainbow trout (Oncorhynchus mykiss) exposed in vivo. Environ Toxicol Chem 18 1492-1497. 

However, the presence of metal in pharmaceuticals, even in trace amounts, is a form of contaminant. For example, metallic ions may act as a catalyst in oxidation that may be detected in drug products. High-sensitivity methods and techniques for metal analysis are essential for quality control. The classical method of detecting metal contamination is the heavy metal testing described in the USP. This method is a precipitation test with H2S. The limit is observed by comparing with the standard solution. 

Ciciarelly, R. et al.. Determination of metal traces — a critical review of the pharmacopoeial heavy metal test, Pharmacopeial Forum, 21, 1995, 1638. 

The physical/chemical toxicity tests are of the type specified in many national pharmacopoeia and standards (2), (3), (13) to (19) inclusive, mainly involving tests on aqueous extracts including those already referred to in Table 1. Other typical tests required on the extracts are taste, odour, colour, clarity, chloride, ammonia, organic phosphorus and heavy metal content, and in addition ignition residue-and heavy metal tests are made directly on the PVC compound. Specified limits for some of these tests vary so it would be misleading to state that all of these tests are met in every case but at present we do know that the new extraction resistant compounds have been shown to satisfy BS 2463 (17), DHSS Specifications (18) and DIN 58361 Part 4 (3) for example. 

Regulated heavy metal testing measures the concentrations of regulated metals in the compost soil at the end of the biodegradation testing. 

Regulated heavy metal testing measures the concentrations of regulated metals in the compost soil at the end of the biodegradation testing. The compost samples must have regulated metal concentrations less than prescribed levels, listed in Table 8.3. 

USP National Formulary (NF), General Chapter <231>, Heavy Metals Test, 2012, http //www.usp.org/usp-nl7hot-topics/elemental-impurities. 

The need for the determination of metallic constituents or impurities in pharmaceutical products has, historically, been addressed by ion chromatographic methods or various wet-bench methods (e.g. the USP heavy metals test). As the popularity of atomic spectroscopy has increased, and the equipment has become more affordable, spectroscopy-based techniques have been routinely employed to solve analytical problems in the pharmaceutical industry. Table 1 provides examples of metal determinations in pharmaceutical matrices, using spectroscopic techniques, and the reasons why these analyses are important. Flame atomic absorption spectrometry (FAAS), graphite furnace atomic absorption spectrometry... 

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