An updated and improved method for analysis of omeprazole/esomeprazole and related substances on core‐shell columns was developed using Fusion LC Method Development™. The method was optimized with respect to column type, column temperature, mobile phase pH level, and gradient time. Four different core‐shell columns were examined to develop a method suitable for both high performance‐ and ultra‐high performance liquid chromatography using a Quality by Design approach. The final method offers two alternative columns: Poroshell EC C18 (3.0 × 100 mm, 2.7 µm) or Poroshell HPH (3.0 × 100 mm, 2.7 µm) with the same gradient elution condition and mobile phase composition. Total run time is 18 min with 12 min of gradient elution. Phosphate buffer (15 mM, pH 7.8) is selected as the aqueous mobile phase and acetonitrile as the organic mobile phase. Column temperature is set at 40°C and ultraviolet detection at 302 nm. Furthermore, by studying parameters in a systematic way, an understanding of the effect of the input parameters enhances the method robustness and should allow for regulatory flexibility in terms of post‐approval changes. Compared to the current United States Pharmacopeia method, the updated method is faster, more efficient and performs well above acceptance criteria.

In the last decade, core-shell particles have gained more and more attention in fast liquid chromatography separations due to their comparable performance with fully porous sub-2 μm particles and their significantly lower back pressure. Core-shell particles are made of a solid core surrounded by a shell of classic fully porous material. To embrace the developed core-shell column market and use these columns in pharmaceutical analytical applications, 17 core-shell C columns purchased from various vendors with various dimensions (50 mm × 2.1 mm to 100 mm × 3 mm) and particle sizes (1.6-2.7 μm) were characterized using Tanaka test protocols. Furthermore, four selected active pharmaceutical ingredients were chosen as test probes to investigate the batch to batch reproducibility for core-shell columns of particle size 2.6-2.7 μm, with dimension of 100 × 3 mm and columns of particle size 1.6 μm, with dimension 100 × 2.1 mm under isocratic elution. Columns of particle size 2.6-2.7 μm were also tested under gradient elution conditions. To confirm the claimed comparable efficiency of 2.6 μm core-shell particles as sub-2 μm fully porous particles, column performances of the selected core-shell columns were compared with BEH C , 1.7 μm, a fully porous column material as well.

No abstract

No abstract

Photodegradation of pharmaceutical and agrochemical compounds is an important concern for health and the environment. Amiloride derivatives undergo clean photosubstitution in protic solvents. We have studied this apparent photo-SNAr reaction with a range of experimental and computational techniques. Available evidence points to a mechanism starting with photoexcitation followed by absorption of a second photon to eject an electron to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Final recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon, leading to a weakly aromatic radical cation. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment as well as in protic solvents. There are also strong similarities to a class of increasingly popular synthetic photoredox methods.

No abstract

Photodegradation of pharmaceutical and agrochemical compounds is an important concern for health and the environment. Amiloride derivatives undergo clean photosubstitution in protic solvents. We have studied this apparent photo-SNAr reaction with a range of experimental and computational techniques. Available evidence points to a mechanism starting with photoexcitation followed by absorption of a second photon to eject an electron to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Final recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon, leading to a weakly aromatic radical cation. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment as well as in protic solvents. There are also strong similarities to a class of increasingly popular synthetic photoredox methods.

Photodegradation of pharmaceutical and agrochemical compounds is an important concern for health and the environment. Amiloride derivatives undergo clean photosubstitution in protic solvents. We have studied this apparent photo-SNAr reaction with a range of experimental and computational techniques. Available evidence points to a mechanism starting with photoexcitation followed by absorption of a second photon to eject an electron to give a radical cation intermediate. Subsequent substitution reaction with the protic solvent is assisted by a general base, possibly strengthened by the proximal solvated electron. Final recombination with the solvated electron generates the observed product. Quantum chemical computations reveal that excited state antiaromaticity is relieved when an electron is ejected from the photoexcited molecule by the second photon, leading to a weakly aromatic radical cation. The mechanism indicated here could have wide applicability to photoinduced degradation of similar heteroaromatic compounds in the environment as well as in protic solvents. There are also strong similarities to a class of increasingly popular synthetic photoredox methods.