Rapid and Comprehensive Impurity Profiling of Synthetic Thyroxine by Ultrahigh-Performance Liquid Chromatography–High-Resolution Mass Spectrometry

Rapid and efficient quality control according to the public authority regulations is mandatory to guarantee safety of the pharmaceuticals and to save resources in the pharmaceutical industry. In the case of so-called "grandfather products" like the synthetic thyroid hormone thyroxine, strict regulations enforce a detailed chemical analysis in order to characterize potentially toxic or pharmacologically relevant impurities. We report a straightforward workflow for the comprehensive impurity profiling of synthetic thyroid hormones and impurities employing ultrahigh-performance liquid chromatography (UHPLC) hyphenated to high-resolution mass spectrometry (HRMS). Five different batches of synthetic thyroxin were analyzed resulting in the detection of 71 impurities within 3 min total analysis time. Structural elucidation of the compounds was accomplished via a combination of accurate mass measurements, computer based calculations of molecular formulas, multistage high-resolution mass spectrometry (HRMS(n)), and nuclear magnetic resonance spectroscopy, which enabled the identification of 71 impurities, of which 47 have been unknown so far. Thirty of the latter were structurally elucidated, including products of deiodination, aliphatic chain oxidation, as well as dimeric compounds as new class of thyroid hormone derivatives. Limits of detection for the thyroid compounds were in the 6 ng/mL range for negative electrospray ionization mass spectrometric detection in full scan mode. Within day and day-to-day repeatabilities of retention times and peak areas were below 0.5% and 3.5% R.SD. The performance characteristics of the method in terms of robustness and information content clearly show that UHPLC-HRMS is adequate for the rapid and reliable detection, identification, and semiquantitative determination of trace levels of impurities in synthetic pharmaceuticals

Attempt to detect primordial ²⁴⁴Pu on Earth.

With a half-life of 81.1 Myr, (244)Pu could be both the heaviest and the shortest-lived nuclide present on Earth as a relic of the last supernova(e) that occurred before the formation of the Solar System. Hoffman et al. [Nature (London) 234, 132 (1971)] reported on the detection of this nuclide (1.0 x 10(-18) g (244)Pu/g) in the rare-earth mineral bastnasite with the use of a mass spectrometer. Up to now these findings were never reassessed. We describe the search for primordial (244)Pu in a sample of bastnasite with the method of accelerator mass spectrometry (AMS). It was performed with a highly sensitive setup, identifying the ions by the determination of their time-of-flight and energy. Using AMS, the stripping to high charge states allows the suppression of any molecular interference. During our measurements we observed no event of (244)Pu. Therefore, we can give an upper limit for the abundance of (244)Pu in our sample of the mineral bastnasite of 370 atoms per gram (1.5 x 10(-19) g (244)Pu/g). The concentration of (244)Pu in our sample of bastnasite is significantly lower than the previously determined value

A new value for the half-life of ¹⁰Be by heavy-ion elastic recoil detection and liquid scintillation counting.

The importance of 10Be in different applications of accelerator mass spectrometry (AMS) is well-known. In this context the half-life of 10Be has a crucial impact, and an accurate and precise determination of the half-life is a prerequisite for many of the applications of 10Be in cosmic-ray and earth science research. Recently, the value of the 10Be half-life has been the centre of much debate. In order to overcome uncertainties inherent in previous determinations, we introduced a new method of high accuracy and precision. An aliquot of our highly enriched 10Be master solution was serially diluted with increasing well-known masses of 9Be. We then determined the initial 10Be concentration by least square fit to the series of measurements of the resultant 10Be/9Be ratio. In order to minimize uncertainties because of mass bias which plague other low-energy mass spectrometric methods, we used for the first time Heavy-Ion Elastic Recoil Detection (HI-ERD) for the determination of the 10Be/9Be isotopic ratios, a technique which does not suffer from difficult to control mass fractionation. The specific activity of the master solution was measured by means of accurate liquid scintillation counting (LSC). The resultant combination of the 10Be concentration and activity yields a 10Be half-life of T1/2 = 1.388 ± 0.018 (1 s, 1.30%) Ma. In a parallel but independent study (Chmeleff et al. [11]), found a value of 1.386 ± 0.016 (1.15%) Ma. Our recommended weighted mean and mean standard error for the new value for 10Be half-life based on these two independent measurements is 1.387 ± 0.012 (0.87%) Ma

A new value for the half-life of 10Be by Heavy-Ion Elastic Recoil Detection and liquid scintillation counting

The importance of 10Be in different applications of accelerator mass spectrometry (AMS) is well-known. In this context the half-life of 10Be has a crucial impact, and an accurate and precise determination of the half-life is a prerequisite for many of the applications of 10Be in cosmic-ray and earth science research. Recently, the value of the 10Be half-life has been the centre of much debate. In order to overcome uncertainties inherent in previous determinations, we introduced a new method of high accuracy and precision. An aliquot of our highly enriched 10Be master solution was serially diluted with increasing well-known masses of 9Be. We then determined the initial 10Be concentration by least square fit to the series of measurements of the resultant 10Be/9Be ratio. In order to minimize uncertainties because of mass bias which plague other low-energy mass spectrometric methods, we used for the first time Heavy-Ion Elastic Recoil Detection (HI-ERD) for the determination of the 10Be/9Be isotopic ratios, a technique which does not suffer from difficult to control mass fractionation. The specific activity of the master solution was measured by means of accurate liquid scintillation counting (LSC). The resultant combination of the 10Be concentration and activity yields a 10Be half-life of T1/2 = 1.388 ± 0.018 (1 s, 1.30%) Ma. In a parallel but independent study (Chmeleff et al. [11]), found a value of 1.386 ± 0.016 (1.15%) Ma. Our recommended weighted mean and mean standard error for the new value for 10Be half-life based on these two independent measurements is 1.387 ± 0.012 (0.87%) Ma