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Introduction: Triterpene acids from the dried sclerotia of Poria cocos (Schw.) Wolf (poria) were recently found to possess anti‐cancer activities. Identification of more triterpene acid analogues in poria is worthwhile for high throughput screening in anti‐cancer drug discovery. Objective: To establish an efficient dereplication strategy for identifying triterpene acid analogues in poria based on ultra‐performance liquid chromatography with electrospray ionisation quadrupole time‐of‐flight tandem mass spectrometry (UPLC‐ESI‐QTOF‐MS/MS). Methodology: The structural characteristics and mass spectrometric data profiles of known triterpene acids previously reported in poria were used to establish a predicted‐analogue database. Then, the quasi‐molecular ions of components in a poria extract were automatically compared with those in the predicted‐analogue database to highlight compounds of potential interest. Tentative structural identification of the compounds of potential interest and discrimination of isomers were achieved by assessing ion fragmentation patterns and chromatographic behaviour prediction based on structure–retention relationship. Results: A total of 62 triterpene acids were unequivocally or tentatively characterised from poria, among which 17 triterpene acids were tentatively identified for the first time in poria. Conclusion: This study provided more structure information of triterpene acids in poria for future high throughput screening of anti‐cancer candidates. It is suggested that this semi‐automated approach in which MS data are automatically compared to a predictive database may also be applicable for efficient screening of other herbal medicines for structural analogues of proven bioactives. An efficient dereplication strategy was established for identifying triterpene acid analogues in poria using UPLC‐ESI‐QTOF MS/MS. This strategy combined analogue prediction‐based selective filtering, fragmentation pattern analysis and chromatographic behaviour prediction. A total of 62 triterpene acids were unequivocally or tentatively characterised from poria, among which 17 triterpene acids were tentatively identified for the first time in poria. [ABSTRACT FROM AUTHOR]

Efficient quantification of fatty-acid (FA) composition (fatty-acidome) in biological samples is crucial for understanding physiology and pathophysiology in large population cohorts. Here, we report a rapid GC-FID/MS method for simultaneous quantification of all FAs in numerous biological matrices. Within eight minutes, this method enabled simultaneous quantification of 50 FAs as fatty-acid methyl esters (FAMEs) in femtomole levels following the efficient transformation of FAs in all lipids including FFAs, cholesterol-esters, glycerides, phospholipids and sphingolipids. The method showed satisfactory inter-day and intra-day precision, stability and linearity (R 2 > 0.994) within a concentration range of 2-3 orders of magnitude. FAs were then quantified in typical multiple biological matrices including human biofluids (urine, plasma) and cells, animal intestinal content and tissue samples. We also established a quantitative structure-retention relationship (QSRR) for analytes to accurately predict their retention time and aid their reliable identification. We further developed a novel no-additive retention index (NARI) with endogenous FAMEs reducing inter-batch variations to 15 seconds; such NARI performed better than the alkanes-based classical RI, making meta-analysis possible for data obtained from different batches and platforms. Collectively, this provides an inexpensive high-throughput analytical system for quantitative phenotyping of all FAs in 8-minutes multiple biological matrices in large cohort studies of pathophysiological effects., Competing Interests: Pinghui Liu, Qinsheng Chen, Lianglong Zhang, Chengcheng Ren, Biru Shi, Jingxian Zhang, Shuaiyao Wang, Ziliang Chen, Qi Wang, Hui Xie, Qingxia Huang and Huiru Tang declare that they have no conflict of interest., (© The Author(s) 2023.)

Abstract: Fluoroquinolones are popular class of antibiotics with distinct chemical functionality. Most of them are ampholytes with one chiral center. Stereogeneic center is located either in the side ring of Gatifloxacin (GFLX) or in the quinolone core of Ofloxacin (OFLX). These two amphoteric fluoroquinolones have terminal amino groups in common. The unusual Nadifloxacin (NFLX) is an acidic fluoroquinolone with a core chiral center. Owing to chirality and functionality differences among GFLX, OFLX, and NFLX, we mapped these enantiomers onto structure‐retention relationship. Amount of acetic acid modifier was studied in screened mobile phase and cellulose tris(3‐chloro‐4‐methyl phenyl carbamate) (Lux cellulose‐2) stationary phase. Experimental design of acetic acid% along with column temperature have been applied. Resolution and enantioselectivity have been related to structural features of the studied enantiomers. High amount of acid (0.4%) was optimum for the separation of either side chirality with a proximate amino group (GFLX) or core chirality without basic functionality (NFLX), while low amount (0.2%) is optimum for core chiral center with distal amino group (OFLX). Temperature has no significant effect on resolution and retention of enantiomers except for OFLX. Enantio‐retention explains possible chiral selective and nonselective interactions. The proposed methods have been validated for pharmaceutical analyses. [ABSTRACT FROM AUTHOR]

Bile acids (BAs) are cholesterol metabolites with important biological functions. They undergo extensive host-gut microbial co-metabolisms during the enterohepatic circulation, creating a vast structural diversity and resulting in great challenges to separate and detect them. Based on the bioanalytical reports in the past decade, this work developed three chromatographic gradient methods to separate a total of 48 BA standards on an ethylene-bridged hybrid (BEH) C18 column and high-strength silica (HSS) T3 column and accordingly unraveled the factors affecting the separation and detection of them by liquid chromatography coupled with mass spectrometry (LC-MS). It was shown that both the acidity and ammonium levels in mobile phases reduced the electrospray ionization (ESI) of BAs as anions of [M−H], especially for those unconjugated ones without 12-hydroxylation. It was also found that the retention of taurine conjugates on the BEH C18 column was sensitive to the strength of formic acid and ammonium in mobile phases. By using the volatile buffers with an equivalent ammonium level as mobile phases, we comprehensively demonstrated the effects of the elution pH value on the retention behaviors of BAs on both the BEH C18 column and HSS T3 column. Based on the retention data acquired on a C18 column, we presented the ionization constants (p K ) of various BAs with the widest coverage beyond those of previous reports. When we made attempts to establish the structure-retention relationships (SRRs) of BAs, the lack of discriminative structural descriptors for BA stereoisomers emerged as the bottleneck problem. The methods and results presented in this work are especially useful for the development of reliable, sensitive, high-throughput, and robust LC-MS bioanalytical protocols for the quantitative metabolomic studies. [ABSTRACT FROM AUTHOR]

Unmodified silica gel in combination with two mobile phases, acetone–n-hexane and acetonitrile–dichloromethane, was used in order to evaluate the capability of normal-phase (NP) chromatography on bare silica gel in estimation of lipophilicity of some polyoxygenated steroids. Soczewinski equation coefficients were employed as a measure of lipophilicity. The RM0values obtained in NP-systems were correlated with those derived by extrapolation from reversed-phase (RP) systems. In addition, retention data, i.e., lipophilicity parameters determined in NP systems were compared with logP values calculated by use of several commercial computer programs. The results showed that chromatographic parameters RM0, and m obtained in NP system consisted of silica gel as stationary phase and acetone–n-hexane as mobile phase, are acceptable as the measures of lipophilicity of polyoxygenated steroids. The mechanism of retention was discussed. [ABSTRACT FROM AUTHOR]

A quantitative structure-retention relationship model is built up by CORAL software based on representation of the molecular structure by simplified molecular input line entry system and graphical representation. This model was used for the prediction of linear retention indices of 96 volatiles in cooking rice. The hybrid version of the molecular structure representation by combination of SMILES and the molecular graph provided the best correlation of the prediction for the considered retention indices. The reliability of established model was evaluated using the leave-many-out cross-validation method ( Q = 0.932) as well as by y scrambling that reveals the suitability of the developed model. The results of the present study show that CORAL software can be used to accurately predict of linear retention indices of chemicals in gas chromatography. [ABSTRACT FROM AUTHOR]

Abstract: Physicochemical properties provide reliable guidance in optimization of pharmacological efficiency and ADME profile of small chemical compounds. Their high-throughput determination is regularly based on application of HPLC techniques. In this study CHI and CHI IAM of 32 4-hydroxycoumarin analogs were measured by HPLC with methanol gradient at pHs 2.8 and 7.0. Results were analyzed by PCA in terms of computed descriptors in order to identify space for optimization of their phospholipids affinity and lipophilicity for which predictive software failed to produce reliable estimations. The chromatographic behavior of studied 4-hydroxycoumarins was typical of acidic compounds. The CHI2.8, CHI7.0, CHI IAM2.8 and CHI IAM7.0 values were all considerably cross-correlated in accordance with their prevailing lipophilic character. Structure–retention relationship (SRR) analysis furthermore revealed that H-bond accepting capacity and dipolar interactions with methanol generally shorten their retention times. However, deviations from the linear trends were noticed for R3/R5-substituted derivatives able to form intramolecular contacts with the 4-O(H) group and characterized by more uniform electron density at 2-O and 4-O atoms and quite different acidity/H-bond donating capacity than the rest of derivatives. Thus, CHI and CHI IAM determinations and SRR analysis are fast and efficiently pointed to ways of modifying biological activities of 4-hydroxycoumarins. [Copyright &y& Elsevier]

Immobilization of cell membrane composites such as cholesterol on high-performance liquid chrornalography (HPLC), column packing enables modelling of xenobiotic behcviour by mimicking permeation processes in the human body. The pharmacokinetics of non-steroidal ontiinflammatory drugs (NSAIDs) have been established to be related to their ability to penetrate the lipid bilayer of cell membranes and disrupt protein mediated processes. The potential existence of interaction betwee NDAID and chclesterol has not yet been proven thereby necessitating its in vitro examination using reversed-phase bioaffinity chromatography. The molecular mapping apprcach based on structural descriptors giving evidence of transient complex formation between NSAID-cholesterol is discussed. [ABSTRACT FROM AUTHOR]

Retention parameters of 45 different barbituric acid derivatives were determined on an amide embedded RP silica column (Discovery RP-AmideC16) using non-buffered water–acetonitrile eluent systems. Linear correlation were calculated between the logarithm of the capacity factor and the acetonitrile concentration in the eluent. To determine the retention behavior of barbituric acid derivatives, stepwise regression analysis (SRA) and principal component analysis (PCA) followed by two-dimensional nonlinear and modified nonlinear mapping was used. It can be concluded, the retention of barbituric acid derivatives are governed mainly by the steric parameters of the substituents. Principal component analysis indicated that the barbituric acid derivatives have mixed retention on this amide embedded RP silica column in water–acetonitrile eluent. [Copyright &y& Elsevier]

[Display omitted] • The Gumbel distribution fits very well the chromatographic peak shape. • An empirical equation relates the retention times with the experimental variables. • A combination of quantum chemical parameters correlates with the capacity factor. • The retention mechanism is well suited to structural characteristics and several quantum chemical parameters. Knowledge about the theoretical relationship between the analyte properties and the critical chromatographic parameters is mandatory for a better interpretation of the separation mechanism and a more leisurely development of quantitative studies. In a preliminary stage of this work, we introduce the Gumbel distribution, the extreme value distribution type-I widely used in other fields, as a novel tool for modelling the chromatographic peak shape. Further, we develop mathematical models to evaluate the effect of the experimental variables and various quantum parameters on the chromatographic indices, such as the retention time, capacity factor, asymmetry factor, tailing factor and number of theoretical plates. Finally, we propose a mechanistic behaviour for the chromatographic separation process based on the structure-retention relationship of fifteen selected drugs involving several molecular quantum parameters. [ABSTRACT FROM AUTHOR]