Photodegradation of quetiapine under UVC irradiation in methanol solution was investigated and structural elucidation of its photodegradation products was performed with the use of the reversed phase UHPLC system coupled with accurate mass hybrid ESI-Q-TOF mass spectrometer. During one run all essential data for the determination of photodegradation kinetics and for the structural elucidation of the products was collected with the use of auto MS/MS mode. Five degradation products were found and their masses and formulas were obtained with high accuracy (0.26–5.02 ppm). For all the analyzed compounds, MS/MS fragmentation spectra were also obtained allowing structural elucidation of the unknown degradation products and indicating photodegradation pathways of quetiapine. The main photodegradation product was identified as 2-[2-[4-(5-oxidodibenzo[b,f][1,4]thiazepin-11-yl)-1-piperazinyl]ethoxy]-ethanol and the photodegradation reaction yields the first-order kinetics with the rate constant k = 0.1094 h−1.
Nowadays, chromatographic methods coupled
with mass spectrometry are the most commonly used tools
in metabolomics studies. These methods are currently
being developed and various techniques and strategies are
proposed for the profiling analysis of biological samples.
However, the most important thing used to maximize
the number of entities in the recorded profiles is the
optimization of sample preparation procedure and the data
acquisition method. Therefore, ultra high performance
liquid chromatography coupled with accurate quadrupoletime-
of-flight (Q-TOF) mass spectrometry was used for the
comparison of urine metabolomic profiles obtained by
the use of various spectral data acquisition methods. The
most often used method of registration of metabolomics
data acquisition – TOF (MS) was compared with the fast
polarity switching MS and auto MS/MS methods with the
use of multivariate chemometric analysis (PCA). In all the
cases both ionization mode (positive and negative) were
studied and the number of the identified compounds was
compared. Additionally, various urine sample preparation
procedures were tested and it was found that the addition
of organic solvents to the sample noticeably reduces the
number of entities in the registered profiles. It was also
noticed that the auto MS/MS method is the least efficient
way to register metabolomic profiles.
The LBOZ criterion is an interesting approach for quantifying selectivity during spectrophotometric analysis by measuring the relative uncertainty increase caused by spectral overlapping. Unfortunately, no reference values for pharmaceuticals analysis in the UV region exist. The current paper presents an estimation of the LBOZ distribution as a random variable for binary and ternary drug mixtures. The estimation was done on a representative group of 170 diverse drug-like compounds. Results of the estimation were fitted to the beta and the Johnson distributions. The obtained parameters can be used to examine the “significance” of the spectral overlap by finding the p-value, interpreted as a chance to obtain higher uncertainty increase among the drugs.
Ultra high performance liquid chromatography (UHPLC), coupled with accurate quadrupole-time-of-flight (Q-TOF) mass spectrometry, was used for the stability study of acetylsalicylic acid within a variety of different organic solutions: methanol, ethanol, propan-2-ol, acetonitrile, tetrahydrofuran and 1,4-dioxane. With the use of gradient elution chromatography and mass spectrometry detection in negative ionization, MS and MS/MS spectra were recorded simultaneously. In addition, quantitative, as well as qualitative analysis was performed during one assay. The stability of acetylsalicylic acid in such solutions was tested at room temperature, in a 12h period. In the work, in all cases, only one main degradation product, salicylic acid, was found. What is more, the work revealed that the degradation of aspirin in the tested organic solutions yields apparent second-order kinetics. The study also demonstrated that acetonitrile and 1,4-dioxane turned out to be the most stable solvents, and an above 80% of initial concentration of acetylsalicylic acid was found in this case. Furthermore, the most popular analytical solvents, methanol and ethanol, were found to be very unstable media. Herein, below 40% of initial concentration of acetylsalicylic acid was seen after 12h. The obtained results were also compared with the degradation of acetylsalicylic acid in a water solution. In this situation, only about 25% of the analyzed compound was resolved to salicylic acid in the same time frame.
The lipophilicity of thirty-two novel acetylcholinesterase (AChE) inhibitors — 1,2,3,4-tetrahydroacridine and 2,3-dihydro-1H-cyclopenta[b]quinoline derivatives was studied by thin layer chromatography. The analyzed compounds were chromatographed on RP-18, RP-8, RP-2, CN and NH2 stationary phases with dioxane — citric buffer pH 3.0 binary mobile phases containing different proportions of dioxane. RM values for pure water were extrapolated from the linear Soczewiński-Wachtmeister equation and six compounds with known literature log P values were used as reference calibration data set for computation of experimental log P values. The obtained results were compared with computationally calculated partition coefficients values (AlogPs, AClogP, AlogP, MlogP, KOWWIN, XlogP2, XlogP3) by PCA and significant differences between them were observed.