Journal of Pharmaceutical Analysis

Nanodiamonds with powerful ability for drug delivery and biomedical applications: Recent updates on in vivo study and patents

Swati Chauhan, Neha Jain, Upendra Nagaich

2020, 10(1): 1-12.

Abstract(274) PDF(7)

Abstract:
Nanodiamonds are novel nanosized carbon building blocks possessing varied fascinating mechanical, chemical, optical and biological properties, making them significant active moiety carriers for biomedical application. These are known as the most'captivating' crystals attributed to their chemical inertness and unique properties posing them useful for variety of applications in biomedical era. Alongside, it becomes increasingly important to find, ascertain and circumvent the negative aspects associated with nano-diamonds. Surface modification or functionalization with biological molecules plays a significant role in managing the toxic behavior since nanodiamonds have tailorable surface chemistry. To take advantage of nanodiamond potential in drug delivery, focus has to be laid on its purity, surface chemistry and other considerations which may directly or indirectly affect drug adsorption on nanodiamond and drug release in biological environment. This review emphasizes on the basic properties, synthesis techniques, surface modification techniques, toxicity issues and biomedical applications of nanodiamonds. For the devel-opment of nanodiamonds as an effective dosage form, researchers are still engaged in the in-depth study of nanodiamonds and their effect on life interfaces.

Karacoline, identified by network pharmacology, reduces degradation of the extracellular matrix in intervertebral disc degeneration via the NF-κB signaling pathway

Xiaoli Zhou, Yingying Hong, Yulin Zhan

2020, 10(1): 13-22.

Abstract(141) PDF(11)

Abstract:
Karacoline is a compound found in the plant Aconitum kusnezoffii Reichb. Although Aconitum kusnezoffii Reichb is widely used for the treatment of pain, very few studies have been carried out on the use of karacoline due to its potential toxicity. In this study, we selected key matrix metalloproteinases (MMPs), collagen II, and aggrecan as targets due to their association with intervertebral disc degeneration (IDD). Using these targets, we then used network pharmacology to predict a series of molecules that might exert therapeutic effects on IDD. Of these molecules, karacoline was predicted to have the best effect. Tumor necrosis factor (TNF)-αis known to promote the degeneration of the extracellular matrix in IDD. We therefore applied different concentrations of karacoline (0, 1.25, or 12.88μM) along with 100 ng/mL TNF-αto rat nucleus pulposus cells and found that karacoline reduced the expression of MMP-14 in IDD by inhibiting the nuclear factor (NF)-κB pathway, while collagen II and aggrecan expression was increased. This suggested that extracellular matrix degradation was inhibited by karacoline (P<0.05). Our data therefore reveal a new clinical application of karacoline and provide support for the use of network pharmacology in predicting novel drugs.

Comparing different domains of analysis for the characterisation of N-glycans on monoclonal antibodies

Sara Carillo, Raquel Pérez-Robles, Craig Jakes, Meire Ribeiro da Silva, Silvia Millán Martín, Amy Farrell, Natalia Navas, Jonathan Bones

2020, 10(1): 23-34.

Abstract(94) PDF(3)

Abstract:
With the size of the biopharmaceutical market exponentially increasing, there is an aligned growth in the importance of data-rich analyses, not only to assess drug product safety but also to assist drug development driven by the deeper understanding of structure/function relationships. In monoclonal antibodies, many functions are regulated by N-glycans present in the constant region of the heavy chains and their mechanisms of action are not completely known. The importance of their function focuses analytical research efforts on the development of robust, accurate and fast methods to support drug development and quality control. Released N-glycan analysis is considered as the gold standard for glycosylation characterisation;however, it is not the only method for quantitative analysis of glycoform heterogeneity. In this study, ten different analytical workflows for N-glycan analysis were compared using four monoclonal antibodies. While observing good comparability between the quantitative results generated, it was possible to appreciate the advantages and disadvantages of each technique and to summarise all the observations to guide the choice of the most appropriate analytical workflow ac-cording to application and the desired depth of data generated.

Rapid identification of chemical profile in Gandou decoction by UPLC-Q-TOF-MSE coupled with novel informatics UNIFI platform

Li Xu a Yi Liu, Hongfei Wu, Huan Wu, Xiaochuang Liu, An Zhou

2020, 10(1): 35-48.

Abstract(386) PDF(13)

Abstract:
Gandou decoction (GDD), a well-known traditional Chinese medicine (TCM) formula, has been widely used for decades to treat Wilson's disease (WD) in China due to its remarkable clinical effects. However, the chemical constituents of GDD still remain unclear because of their complexity. In this work, a reliable and sensitive strategy based on ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) and UNIFI informatics platform was applied to investigate the chemical components in GDD. In total, 96 compounds including anthraqui-nones, alkaloids, protostane triterpenoids, flavonoids, triterpenoid saponins, tannins, curcuminoids, etc, were identified or tentatively characterized from GDD by comparing their retention time, accurate mass within 5 ppm error and MSE fragmentation patterns. Among them, eleven compounds were confirmed unambiguously with reference standards. Representative compounds in different chemical structure types were analyzed in fragmentation patterns and characteristic ions. Moreover, to better understand the chemical contribution of individual herbs to the whole decoction, the corresponding each herb in GDD was also detected. This study developed a rapid method for characterizing the chemical constitu-ents in GDD, which could not only be used for chemical standardization and quality control, but also be helpful for further research of GDD in vivo.

GC-NICI-MS analysis of acetazolamide and other sulfonamide (R-SO2-NH2) drugs as pentafluorobenzyl derivatives [R-SO2-N(PFB)2] and quantification of pharmacological acetazolamide in human urine

Olga Begou, Kathrin Drabert, Georgios Theodoridis, Dimitrios Tsikas

2020, 10(1): 49-59.

Abstract(98) PDF(2)

Abstract:
Acetazolamide (molecular mass (MM), 222) belongs to the class of sulfonamides (R-SO2-NH2) and is one of the strongest pharmacological inhibitors of carbonic anhydrase activity. Acetazolamide is excreted unchanged in the urine. Here, we report on the development, validation and biomedical application of a stable-isotope dilution GC-MS method for the reliable quantitative determination of acetazolamide in human urine. The method is based on evaporation to dryness of 50 μL urine aliquots, base-catalyzed derivatization of acetazolamide (d0-AZM) and its internal standard [acetylo-2H3]acetazolamide (d3-AZM) in 30 vol% pentafluorobenzyl (PFB) bromide in acetonitrile (60 min, 30 °C), reconstitution in toluene (200μL) and injection of 1-μL aliquots. The negative-ion chemical ionization (NICI) mass spectra (methane) of the PFB derivatives contained several intense ions including [M]- at m/z 581 for d0-AZM and m/z 584 for d3-AZM, suggesting derivatization of their sulfonamide groups to form N,N-dipenta-fluorobenzyl derivatives (R-SO2-N(PFB)2), i.e., d0-AZM-(PFB)2 and d3-AZM-(PFB)2, respectively. Quanti-fication was performed by selected-ion monitoring of m/z 581 and 83 for d0-AZM-(PFB)2 and m/z 584 and 86 for d3-AZM-(PFB)2. The limits of detection and quantitation of the method were determined to be 300 fmol (67 pg) and 1μM of acetazolamide, respectively. Intra-and inter-assay precision and accuracy for acetazolamide in human urine samples in pharmacologically relevant concentration ranges were determined to be 0.3%-4.2%and 95.3%-109%, respectively. The method was applied to measure urinary acetazolamide excretion after ingestion of a 250 mg acetazolamide-containing tablet (Acemit?) by a healthy volunteer. Among other tested sulfonamide drugs, methazolamide (MM, 236) was also found to form a N,N-dipentafluorobenzyl derivative, whereas dorzolamide (MM, 324) was hardly detectable. No GC-MS peaks were obtained from the PFB bromide derivatization of hydrochlorothiazide (MM, 298), xipamide (MM, 355), indapamide and metholazone (MM, 366 each) or brinzolamide (MM, 384). We demonstrate for the first time that sulfonamide drugs can be derivatized with PFB bromide and quan-titated by GC-MS. Sulfonamides with MM larger than 236 are likely to be derivatized by PFB bromide but to lack thermal stability.

Analysis of pesticide residues in commercially available chenpi using a modified QuEChERS method and GC-MS/MS determination

Shuang Li, Peipei Yu, Ceng Zhou, Ling Tong, Dongxiang Li, Zhiguo Yu, Yunli Zhao

2020, 10(1): 60-69.

Abstract(161) PDF(1)

Abstract:
To ensure the safety of the commercially available chenpi, a convenient and fast analytical method was developed for the determination of 133 pesticide residues in chenpi using gas chromatography-tandem mass spectrometry (GC-MS/MS). In this study, different extraction solvents, redissolution solvents and adsorbents were tested according to the recovery and purification effect to obtain a modified QuEChERS method. The samples were extracted with acetonitrile. During the clean-up step, octadecyl-modified silica (C18) and graphitized carbon black (GCB) were selected, and aminopropyl (NH2) was used instead of primary secondary amine (PSA) because of its weaker ion exchange capacity which had little effect on the recovery of ditalimfos. Samples were quantified by matrix-matched calibration with internal stan-dards. All pesticides showed good linearity in the respective range, both with values of r2 >0.99. The average recoveries of the pesticides spiked samples ranged from 70.0% to 112.2% with the RSDs of 0.2%–14.4%. The modified QuEChERS method was validated and applied to twenty real samples. Five pesticides were found in eight batches, but no pesticide exceeded the maximum residue limits (MRL, MRL reference to European commission).

Determination of L-norvaline and L-tryptophan in dietary supplements by nano-LC using an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine-silica hybrid monolithic column

Dongsheng Xu, Elena Sánchez-López, Qiqin Wang, Zhengjin Jiang, María Luisa Marina

2020, 10(1): 70-77.

Abstract(132) PDF(4)

Abstract:
An analytical methodology based on an O-[2-(methacryloyloxy)-ethylcarbamoyl]-10,11-dihydroquinidine (MQD)-silica hybrid monolithic column was developed for the enantioseparation of 9-fluorenylmethoxycarbonyl (FMOC) derivatized amino acids by nano-liquid chromatography. The mo-bile phase was optimized including the apparent pH, content of ACN, and concentration of the buffer to obtain a satisfactory enantioresolution performance. 27 FMOC derivatized amino acids including 19 protein and 8 non-protein amino acids were tested, and 19 out of them were enantiomerically discriminated obtaining baseline separation for 11 of them. Analytical characteristics of the method were evaluated for norvaline and tryptophan in terms of linearity, precision, accuracy, limits of detection (LOD) and quantitation (LOQ) showing good performance to be applied to the enantiomeric determination of these amino acids in dietary supplements. LOD and LOQ values were 9.3 and 31μM for norvaline en-antiomers and 7.5 and 25μM for tryptophan enantiomers, respectively. The contents of D-norvaline and D-tryptophan were below their respective LODs in all the analyzed samples. Quantitation of L-tryptophan and L-norvaline showed good agreement with the labeled contents except for one sample which did not show presence of L-norvaline, contrary to the label indication.

Thermodynamics of clay-drug complex dispersions: Isothermal titration calorimetry and high-performance liquid chromatography

Ana-Maria Totea, Juan Sabin, Irina Dorin, Karl Hemming, Peter R. Laity, Barbara R. Conway, Laura Waters, Kofi Asare-Addo

2020, 10(1): 78-85.

Abstract(142) PDF(1)

Abstract:
An understanding of the thermodynamics of the complexation process utilized in sustaining drug release in clay matrices is of great importance. Several characterisation techniques as well as isothermal calo-rimetry were utilized in investigating the adsorption process of a model cationic drug (diltiazem hy-drochloride, DIL) onto a pharmaceutical clay system (magnesium aluminium silicate, MAS). X-ray powder diffraction (XRPD), attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) and optical microscopy confirmed the successful formation of the DIL-MAS complexes. Drug quantification from the complexes demonstrated variable behaviour in the differing media used with DIL degrading to desacetyl diltiazem hydrochloride (DC-DIL) in the 2 M HCl media. Here also, the authors report for the first time two binding processes that occurred for DIL and MAS. A competitor binding model was thus proposed and the thermodynamics obtained suggested their binding processes to be enthalpy driven and entropically unfavourable. This information is of great importance for a formulator as care and consideration should be given with appropriate media selection as well as the nature of binding in complexes.

Trace determination and characterization of ginsenosides in rat plasma through magnetic dispersive solid-phase extraction based on core-shell polydopamine-coated magnetic nanoparticles

Ningning Zhao, Shu Liu, Junpeng Xing, Zifeng Pi, Fengrui Song, Zhiqiang Liu

2020, 10(1): 86-96.

Abstract(160) PDF(2)

Abstract:
Enrichment of trace bioactive constituents and metabolites from complex biological samples is chal-lenging. This study presented a one-pot synthesis of magnetic polydopamine nanoparticles (Fe3O4@-SiO2@PDA NPs) with multiple recognition sites for the magnetic dispersive solid-phase extraction (MDSPE) of ginsenosides from rat plasma treated with white ginseng. The extracted ginsenosides were characterized by combining an ultra-high-performance liquid chromatography coupled to a high-resolution mass spectrometry with supplemental UNIFI libraries. Response surface methodology was statistically used to optimize the extraction procedure of the ginsenosides. The reusability of Fe3O4@-SiO2@PDA NPs was also examined and the results showed that the recovery rate exceeded 80% after recycling 6 times. Furthermore, the proposed method showed greater enrichment efficiency and could rapidly determine and characterize 23 ginsenoside prototypes and metabolites from plasma. In com-parison, conventional methanol method can only detect 8 ginsenosides from the same plasma samples. The proposed approach can provide methodological reference for the trace determination and charac-terization of different bioactive ingredients and metabolites of traditional Chinese medicines and food.

Instructions to Authors Journal of Pharmaceutical Analysis

2020, 10(1): 96-97.

Abstract(110) PDF(2)

Abstract:

2020 Vol. 10, No. 1