Journal of Chromatography B (v.915-916, #C)
Editorial Board (i).
High-sensitivity liquid chromatography–tandem mass spectrometry method for the simultaneous determination of sodium picosulfate and its three major metabolites in human plasma by Yong Yang; Jinghua Yu; Youming Lu; Yu Xia; Dafang Zhong; Xiaoyan Chen (1-7).
► An LC/MS/MS method for simultaneous assay PICO and its metabolites in human plasma. ► In-source conversion interferences of conjugated compounds were avoided by chromatography separation. ► Reference standards for M1, M2 and their deuterium labeled ISs were in-house synthesized. ► Deuterium labeled ISs were used to improve the reproducibility. ► The pharmacokinetic profiles of PICO, M1, and M2 in humans were firstly characterized.Sodium picosulfate (PICO-Na) is a member of the polyphenolic group of stimulant laxatives. Its major metabolites in humans are its active aglycone BHPM (bis-(p-hydroxyphenyl)-pyridyl-2-methane), the monoglucuronide (M1) and the monosulfate (M2) of BHPM. A sensitive, specific and rapid liquid chromatography–tandem mass spectrometry method was established and validated for the simultaneous determination of picosulfate (PICO) and its three major metabolites in human plasma to investigate the pharmacokinetics of PICO and its major metabolites. Following protein precipitation with acetonitrile, chromatographic separation was achieved on a Luna 5u C18(2) column using gradient elution starting with 10% of 10 mM ammonium acetate followed by increasing percentages of acetonitrile to eliminate interferences due to in-source conversion of the conjugated metabolites. Detection was performed on a tandem mass spectrometer equipped with an electrospray ionization source operated in the positive mode, using the transitions of m/z 438.1 → m/z 278.1 for PICO, m/z 278.1 → m/z 184.2 for BHPM, m/z 454.1 → m/z 184.2 for M1, and m/z 358.1 → m/z 184.2 summed with m/z 358.1 → m/z 278.1 for M2. Deuterium labeled compounds of the analytes were used as the internal standard, two of which, M1-d12 and M2-d12, were synthesized in-house. The method was validated in concentration ranges of 0.150–40.0 ng/mL for PICO and M2, 0.600–160 ng/mL for BHPM, and 0.045–12.0 ng/mL for M1 with acceptable accuracy and precision. The method was successfully applied to characterize the pharmacokinetic profiles of PICO and its metabolites in healthy volunteers after a single oral administration of 5 mg PICO-Na.
Keywords: Sodium picosulfate; Glucuronide conjugate; Sulfate conjugate; LC–MS/MS; Pharmacokinetics;
Simultaneous determination of gastrodin and puerarin in rat plasma by HPLC and the application to their interaction on pharmacokinetics by Li Jiang; Jundong Dai; Zhenlin Huang; Qinghua Du; Jiahao Lin; Yurong Wang (8-12).
► Gas and Pur in rat plasma were determined simultaneously for the first time. ► Gas and Pur will alter the pharmacokinetic parameters of each other. ► The AUC 0–t of Gas and Pur coadministrated increased by 152, 1068%, respectively. ► The MRT of Gas and Pur coadministrated has been prolonged significantly. ► It is indicated that Gas and Pur may enhance the absorption of each other.Gastrodin (Gas) and puerarin (Pur) are bioactive substances derived from traditional Chinese medicine Gastrodia elata and Radix Puerariae, respectively, which were often used together in Chinese clinical prescriptions. Their injections were used in combined way for treatment of some cardiocerebrovascular diseases in clinic, especially for vertigo due to vertebrobasilar ischemia. In this paper, interaction of gastrodin and puerarin in rat plasma pharmacokinetics via intragastic (i.g.)/intravenous (i.v.) administration was investigated. A reliable HPLC method was developed for simultaneous determination of Gas and Pur in rat plasma with a linear range of 0.101–101 μg/mL for Gas and 0.0500–5.98 μg/mL for Pur (r 2 > 0.993). The LLOQ, LOD of Gas and Pur were determined to be 0.101, 0.0486 μg/mL, and 0.05, 0.0245 μg/mL, respectively. The intra-day and inter-day precision were all less than 12.0%, whilst the accuracy were all within 96.4 ± 6.00%. The proposed method has been successfully applied to the pharmacokinetic study of the analytes in rats after i.g./i.v. administration of Gas and Pur alone or combined with each other (i.g.: 40 mg/kg Gas, 400 mg/kg Pur; i.v.: 20 mg/kg Gas, 20 mg/kg Pur). Blood samples were collected from retinal vein plexus of rats at predetermined time points and plasma containing the internal standard tyrosol (IS) were precipitated by methanol and chromatography was carried out on a C18 column with a gradient mobile phase of ACN–H2O with 0.05% phosphoric acid as a modifier. The pharmacokinetic profiles of combined administration were found to be distinct from those of given alone. The C max, T max, T 1/2, MRT of Gas administrated alone or combined with Pur via i.g. were 21.7 μg/mL, 0.250 h, 2.81 h, 0.830 h and 18.4 μg/mL, 0.550 h, 0.970 h, 1.37 h, respectively, of Pur administrated alone or combined with Gas via i.g. were 0.490 μg/mL, 1.95 h, 1.33 h, 2.10 h and 2.01 μg/mL, 0.570 h, 4.00 h, 5.10 h, respectively. The relative oral bioavailability of Pur in combined administration was 10.7 times as much as that of single administration, whilst 1.52 folds in Gas. These results indicate that co-administration of Gas and Pur is a promising combination to gain higher bioavailability and it is suggested that doctors pay more attention to the dosages of the two when simultaneously using both of them.
Keywords: Gastrodin; Puerarin; Interaction; Pharmacokinetics; Oral bioavailability;
Simultaneous determination of carbamate insecticides and mycotoxins in cereals by reversed phase liquid chromatography tandem mass spectrometry using a quick, easy, cheap, effective, rugged and safe extraction procedure by Jin-Ming Zhang; Yin-Liang Wu; Yao-Bin Lu (13-20).
► A LC–MS/MS method was developed for 22 carbamates and 17 mycotoxins in cereals. ► A simple pretreatment procedure based on QuEChERS has been established. ► Selectivity, linearity, trueness, precision, LOD, and LOQ had been validated. ► The whole method was fast, reliable, convenient and sensitive.A simple, sensitive and reliable analytical method was developed for the simultaneous determination of 22 carbamate insecticides and 17 mycotoxins in cereals by ultra high performance liquid chromatography electrospray ionization tandem mass spectrometry (UHPLC–ESI-MS/MS). Carbamates and mycotoxins were extracted from cereal samples using a QuEChERS (Quick, Easy, Cheap, Effective, Rugged and Safe) procedure without any further clean-up step. The extract was diluted with water containing 0.1% formic acid and 5.0 mM ammonium acetate, and analyzed by LC–MS/MS on a Waters Acquity BEH C18 column with water (0.1% formic acid, 0.50 mM ammonium acetate)/methanol as mobile phase with gradient elution. Matrix-matched calibration was used for quantification. Blank samples (rice, wheat and corn) were fortified at 5, 10 and 50 μg/kg except for five zearalenonic compounds at 25, 50 and 250 μg/kg, and recoveries were in the range of 70–120%. Relative standard deviations were lower than 20% in all cases. The LOQ values were in the range of 0.20–29.7 μg/kg. The method is suitable for the simultaneous determination of carbamate insecticides and mycotoxins in cereals. The total time required for the analysis of one sample, including sample preparation, was about 35 min.
Keywords: Carbamate insecticides; Mycotoxins; Cereal; LC–MS/MS; QuEChERS;
Generic detection of basic taxoids in wood of European Yew (Taxus baccata) by liquid chromatography–ion trap mass spectrometry by Geoffrey C. Kite; Emily R. Rowe; Nigel C. Veitch; Jill E. Turner; Elizabeth A. Dauncey (21-27).
► Generic method developed for detecting basic taxoids by LC–MS. ► Basic taxoids detected in heartwood of Taxus baccata (European yew). ► Wine extracts basic taxoids from yew wood. ► It is suggested that wine should not be drunk from vessels made of yew wood.The occurrence of the cardiotoxin taxine (comprising taxine B and several other basic taxoids) in leaves of Taxus baccata L. (European yew) is well known and has led to public concerns about the safety of eating or drinking from utensils crafted from the wood of this poisonous species. The occurrence of basic taxoids in the heartwood of T. baccata had not been examined in detail, although the bark is known to contain 2′β-deacetoxyaustrospicatine. Initial examination of heartwood extracts for 2′β-deacetoxyaustrospicatine by liquid chromatography–mass spectrometry (LC–MS) revealed the presence of this basic taxoid at about 0.0007% dry weight, using a standard isolated from bark. Analyses for taxine B, however, proved negative at the extract concentration analysed. Observing other basic taxoids within the heartwood extracts was facilitated by developing generic LC–MS methods that utilised a fragment arising from the N-containing acyl group of basic taxoids as a reporter ion. Of the various MS strategies available on a hybrid ion trap-orbitrap instrument that allowed observation of this reporter ion, combining all-ion collisions with high resolution ion filtering by the orbitrap was most effective, both in terms of the number of basic taxoids detected and sensitivity. Numerous basic taxoids, in addition to 2′β-deacetoxyaustrospicatine, were revealed by this method in heartwood extracts of T. baccata. Red wine readily extracted the basic taxoids from heartwood while coffee extracted them less efficiently. Contamination with basic taxoids could also be detected in soft cheese that had been spread onto wood. The generic LC–MS method for detecting basic taxoids complements specific methods for detecting taxine B when investigating yew poisoning cases in which the analysis of complex extracts may be required or taxine B has not been detected.
Keywords: Basic taxoid; Taxine; Taxus baccata; Yew; Wood; LC–MS;
Determination of phenylephrine in human plasma using ultra-performance liquid chromatography–tandem mass spectrometry by Sheng Feng; Qian Zhao; Ji Jiang; Pei Hu (28-32).
► Analyte was quantifiable in amounts well below previously reported values. ► The total run time was much fast compared to the literature. ► The method was fully validated and applied successfully in a clinical study.This paper described a sensitive and rapid method based on ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC–MS/MS) for the determination of phenylephrine in human plasma. Plasma samples were pre-purified by solid-phase extraction (SPE). The chromatographic separation was achieved with BEH HILIC column using a mixture of 10 mM pH 3.5 ammonium formate and acetonitrile (10:90, v/v) under isocratic conditions at a flow rate of 0.4 mL/min. The mass spectrometry was carried out using positive electrospray ionization (ESI) and data acquisition was carried out in the multiple reaction monitoring (MRM) mode. The method was fully validated over the concentration range of 10.0–5000 pg/mL. The lower limit of quantification (LLOQ) was 10.0 pg/mL. Inter- and intra-batch precision was less than 15% and the accuracy was within 85–115%. Extraction recovery was 78.5%. Selectivity, matrix effects and stability were also validated. The method was applied to the pharmacokinetic study of phenylephrine hydrochloride in Chinese subjects.
Keywords: Determination; Phenylephrine; UPLC–MS/MS; Human plasma;
Highly efficient enrichment of phosvitin phosphopeptides by novel magnetic carboxymethyl chitosan nanoparticles decorated with Fe (III) ions by Jun Sun; Yuntao Liu; Yujie Su; Wenshui Xia; Yanjun Yang (33-38).
► Immobilized metal affinity magnetic nanoparticles (short as IMANs). ► Phosvitin phosphopeptides (short as PPPs). ► The synthetic route allows preparing high-quality IMAN in a large scale. ► The obtained IMANs (Fe (III)) possess the high PPPs enrichment efficiency. ► The application of the IMAN (Fe (III)) may find much potential in PPPs enrichment.Functional immobilized metal affinity magnetic carboxymethyl chitosan nanoparticles (abbreviated as Fe3O4 (PEG + CM-CTS) @ Fe (III)) were conveniently applied for phosvitin phosphopeptides (PPPs) enrichment for the first time. The morphology of magnetic nanoparticles was observed by transmission electron microscope (TEM). It was found that the diameter of Fe3O4 (PEG + CM-CTS) @ Fe (III) was about 20 nm, and could easily aggregate by a magnet when suspending in the aqueous solution. In the PPPs enrichment study, the results obtained emphasized the role of pH, temperature and the initial concentration of the peptides solution in governing the efficiency and mechanism of affinity interactions. Due to the large specific surface area, the enrichment of PPPs onto the Fe3O4 (PEG + CM-CTS) @ Fe (III) nanoparticles was promising. The adsorption equilibrium of PPPs onto the obtained magnetic nanoparticles fitted well with the Langmuir model, and the nitrogen/phosphorus molar ratio (N/P) which at the maximum enrichment capacity for PPPs was 4.83. Due to the small diameter, the decrease of the N/P is particularly rapid in the early enrichment stages (0–30 min) to reach a plateau after 60 min. Compared with traditional methods, the need for preparation of phosvitin before purification is obviated and PPPs of higher purity were obtained. Since the preparation, surface modification and affinity separation processes of the magnetic nanoparticles are cost-effective, convenient and efficient, this type of Fe3O4 (PEG + CM-CTS) @ Fe (III) nanoparticles would bring advantages compared to conventional separation techniques of PPPs from chicken egg yolk, as well as for phosphopeptides enrichment in proteomics research.
Keywords: Magnetic nanoparticles; Bioactive peptides; Phosvitin; Phosphopeptides;
Sensitive measurement of polyols in urine by capillary zone electrophoresis coupled with amperometric detection using on-column complexation with borate by Shu-li Ge; Huan Wang; Zhi-Fang Wang; Shuang Cheng; Qing-Jiang Wang; Pin-Gang He; Yu-Zhi Fang (39-45).
► A sensitive CZE-AD method for the simultaneous analysis of polyols was developed. ► The polyol isomers were separated on the formation of polyol–borate complexes. ► Some urinary polyols in diabetes patients were higher than those of healthy ones. ► This method can become a choice for recognising abnormal polyols metabolism.Little is known about human polyol metabolism, but recent studies indicate that abnormal polyol concentrations in body fluids are related to several diseases. In this study, a rapid and sensitive method for the determination of seven major polyols in urine including two groups of polyol isomers, C5-polyols (Rib + Arb + Xyl) and C6-polyols (Sor + Gal + Man), was developed using capillary zone electrophoresis coupled with amperometric detection (CZE-AD). The effects of the working electrode potential, pH, running buffer components and concentrations, separation voltage and injection times were investigated. Under the optimised conditions, seven types of polyols could be perfectly separated via the formation of anionic polyol–borate complexes in a borate buffer solution. Highly linear current responses to the polyol concentrations were obtained with good correlation (0.9984 < R 2 < 0.9997), and the limits of detection (LODs) ranged from 1.33 × 10−6 to 5.8 × 10−7 mol L−1 (S/N = 3). The proposed method has been successfully used to detect polyols in urinary samples from healthy subjects and diabetes patients, demonstrating accurate and reliable results. This method has potential applications in the recognition of inborn errors affecting polyol metabolism.
Keywords: Capillary zone electrophoresis; Amperometric detection; Polyols; Borate complexation; Urine;
Magnetic nanoparticles of nitrogen enriched carbon (mnNEC) for analysis of pesticides and metabolites in zebrafish by gas chromatography–mass spectrometry by Youe Zhou; Qian Xia; Mengjie Ding; Hubert Kageruka; Haiying Jiang; Yan Jiang; Huifen Jing; Xiao Xiao; Hongying Zhong (46-51).
► Magnetic nanoparticles of Fe3O4 were coated by in situ polymerization of pyrrole. ► Carbonization of polypyrrole coated magnetic nanoparticles at high temperature and nitrogen atmospheric condition. ► Magnetic nanoparticles of nitrogen enriched carbon (mnNEC) can be readily dispersed in aqueous solutions. ► The mnNEC can be used for enrichment of environmental pollutants such as pesticide residues and metabolites.Nanosized carbon based sorbents have been widely used for separation, enrichment and desalting of biological samples because of their distinguished characteristics. In this work, magnetic nanoparticles of nitrogen enriched carbon (mnNEC) have been developed for enrichment of organochlorine pesticide DDT and metabolite DDE that have been accumulated in zebrafish during the course of environmental exposure. Polymerization of pyrrole was performed in the aqueous suspension of Fe3O4 nanoparticles. Resultant core–shell nanoparticules coated with polypyrrole were then subjected to a process of carbonization under high temperature and nitrogen atmospheric condition. The presence of nitrogen atoms in carbon nanoparticles increases the hydrophilicity and dispersability in aqueous samples. It has been experimentally demonstrated that mnNEC can be effectively dispersed in aqueous samples and rapidly isolated by the application of an external magnetic field. Recoveries of DDT and DDE from water range from 90% to 102% and 85–97% respectively. In combination with Selected Ion Monitoring (SIM) experiments of gas chromatography–mass spectrometry, the detection limit can be down to low ng/mL level. By using mnNEC approach, two interesting results have been found for zebrafish with 60 days exposure to DDT (1 μg/l). (1) There is higher concentration of DDT (37–143 ng/g) and DDE (173–1108 ng/g) in male zebrafish body tissues than that of female (7–52 ng/g and 146–362 ng/g for DDT and DDE respectively). (2) There is high ratio of DDE/DDT for both female and male zebrafish, implying high environmental persistence and ongoing bioaccumulation.
Keywords: Nitrogen-enriched carbon; Magnetic nanoparticles; Polypyrrole; Carbonization; Gas chromatography–mass spectrometry;
Simultaneous quantification of individual intermediate steroids in silkworm ecdysone biosynthesis by liquid chromatography–tandem mass spectrometry with multiple reaction monitoring by Juri Hikiba; Mari H. Ogihara; Masatoshi Iga; Kazuki Saito; Yoshinori Fujimoto; Minoru Suzuki; Hiroshi Kataoka (52-56).
► A quantification method for intermediates in ecdysone biosynthesis was developed. ► The method employs the LC–MS/MS with multiple reaction monitoring. ► All of the intermediate ecdysteroids can be quantified simultaneously. ► The method's sensitivity is comparable to those of conventional RIA and ELISA. ► The method was applied to biological samples from silkworms during their life cycle.The concentration changes of endogenous ecdysteroids are closely related to the regulation of insect growth and development. Although they are frequently measured by immunoassays with anti-steroid antibodies, the separate estimations of the individual concentrations of ecdysone and other ecdysteroids with similar chemical structures are quite difficult to accomplish. In this study, an efficient method for the simultaneous, individual quantification of intermediate steroids in ecdysone biosynthesis was developed, using LC–MS/MS. By employing multiple reaction monitoring (MRM) in the MS detection, the selectivity and sensitivity of the method were greatly enhanced, allowing the estimation of trace amounts of steroids in biological samples from silkworm prothoracic glands and hemolymph.
Keywords: Ecdysteroid biosynthesis; LC–MS/MS; Multiple reaction monitoring (MRM); Silkworm prothoracic glands and hemolymph; Simultaneous quantification;
The effect of various S-alkylating agents on the chromatographic behavior of cysteine-containing peptides in reversed-phase chromatography by Xuehui Jiang; Dmitry Shamshurin; Vic Spicer; Oleg V. Krokhin (57-63).
► Chromatographic behavior of cysteine-containing peptides with 6 different alkylation chemistries has been investigated under 3 different reversed-phase HPLC conditions ► Peptide's retention is strongly affected by the charge state of the side chain ► Peptide retention prediction models should be modified to accommodate changes in the alkylation status of Cys.We investigate the influence of various alkylation chemistries on the reversed phase (RP) HPLC behavior of Cys-containing peptides under the most popular RP-HPLC conditions used in proteomics: C18 phases with trifluoroacetic acid (TFA) or formic acid (FA) as the ion pairing modifiers, and separation at pH 10. Akylating agents studied are iodoacetamide (IAM), iodoacetic acid (IAA), 4-vinylpyridine (4-VP), acrylamide (AA) and methyl methanethiosulfonate (MMTS). These were compared against the retention of identical peptides without alkylation, i.e. free cysteines. The intrinsic hydrophobicity values of the Cys residue under formic acid conditions for these modifications were found to increase in the following order: 4-VP < IAM < AA < IAA < free Cys < MMTS. The retention contribution of the positively charged 4-VP derivative is affected by the nature of the ion-pairing modifier; this is the most hydrophilic residue for formic acid based eluents, and second most hydrophilic behind IAM-alkylated Cys using TFA eluent. Switching to a basic condition dramatically decreases the retention of free cysteine and IAA-alkylated analytes due to the ionization of side-chains. The opposite effect is observed for 4-VP, which become neutral at basic pHs. The careful measurement of the hydrophobic contributions for these residues is vital to the development of accurate peptide retention prediction models; the incorporation of these modifications into our Sequence Specific Retention Calculator model is presented.
Keywords: Peptide reversed-phase HPLC; Chemically modified peptides; Peptide retention prediction; Cysteine alkylation;
A HPLC method for simultaneous determination of 5-aminoimidazole-4-carboxamide riboside and its active metabolite 5-aminoimidazole-4-carboxamide ribotide in tumor-bearing nude mice plasma and its application to pharmacokinetics study by Xiaoliang Cheng; Liping Guo; Zaiquan Li; Liang Li; Tianyan Zhou; Wei Lu (64-70).
► A HPLC method for simultaneous assay of AICA riboside and AICA ribotide was developed. ► This HPLC method involved on-line solid phase extraction and column switching. ► The method was applied to pharmacokinetics study of AICA riboside and AICA ribotide.A HPLC method with on-line solid phase extraction (SPE) and column switching was developed for simultaneous determination of 5-aminoimidazole-4-carboxamide riboside (AICA riboside) and its active metabolite 5-aminoimidazole-4-carboxamide ribotide (AICA ribotide) in nude mice plasma. Plasma sample was deproteinized by adding a half volume of 10% trichloroacetic acid (TCA), and the resulting supernatant was extracted with diethyl ether to remove TCA. 50 μl aqueous fraction was injected onto a WAX-1 SPE column, and AICA ribotide was trapped on the SPE column, while AICA riboside was eluted from the SPE column. The chromatographic separation of AICA riboside was achieved on CG16 column, and separation of AICA ribotide was performed on HILIC-10 and WAX-1 column. The columns temperature was maintained at 40 °C, and the optimal detection wavelength was 268 nm for both AICA riboside and AICA ribotide. The total analytical run time was 40 min. The proposed method was linear over the range of 0.1–500 μg/ml for AICA riboside and 0.03–50 μg/ml for AICA ribotide. The lower limit of quantification (LLOQ) was 100 and 30 ng/ml for AICA riboside and AICA ribotide, respectively. The sensitivity, accuracy and precision of this method were within acceptable limits during validation period. The method was successfully applied to investigate the pharmacokinetics characteristics of AICA riboside and its active metabolite AICA ribotide in nude mice bearing MCF-7 cell xenografts.
Keywords: 5-Aminoimidazole-4-carboxamide riboside; 5-Aminoimidazole-4-carboxamide ribotide; HPLC; Solid phase extraction; Column switching;
Simultaneous measurement of doxorubicin and reduced metabolite doxorubicinol by UHPLC–MS/MS in human plasma of HCC patients treated with TACE by Cristina Sottani; Guido Poggi; Fabio Melchiorre; Benedetta Montagna; Claudio Minoia (71-78).
► Developed method for DOX and DOXol determination in human plasma samples. ► The UHPLC–MS/MS method was FDA validated. ► Doxorubicin was pre-loaded in microspheres and administered by TACE procedure. ► The method was applied to HCC patients. ► First PK profiles of DOX and DOXol in chemoembolization procedures were achieved.A sensitive, selective, accurate and precise method for simultaneous quantification of doxorubicin (DOX) and doxorubicinol (DOXol) in human plasma of patients diagnosed as having intermediate stage unresectable hepatocellular carcinoma (HCC) was developed. The method was based on electrospray tandem mass spectrometry in selected reaction monitoring mode. DOX, DOXol and trofosfamide, an internal standard, were extracted from plasma by using a simple solid phase extraction (SPE) procedure after the addition of 0.1 M hydrochloric acid.A 200-μL aliquot of the extracted sample reconstituted in mobile phase was analyzed on a Zorbax SB-C18 UHPLC column (50 mm × 2.1 mm, 1.8 μm particle size) in 8 min. The mobile phase consisted of acetonitrile and 0.1% formic acid pH 4.5 (95:05 v/v). Good accuracy and precision of this method were demonstrated by determination of spiked plasma QC samples in four consecutive days. The SPE extraction recoveries ranged from 72.3 to 77.3% and 75.5 to 98.4% for doxorubicin and doxorubicinol, respectively. The intra-day and inter-day precisions were less than 11.4%. The limit of quantitation was 1.0 ng/mL for both compounds. The calibration curves of DOX and DOXol were analyzed by weighted linear regression with 1/x as a weighting factor. They were linear over the concentration range of 1.0–100.0 ng/mL with R 2 greater than 0.99.This developed method was successfully applied to study plasma pharmacokinetics in patients affected by HCC and treated with transarterial chemoemolization practices (TACEs) using HepaSphere™ pre-loaded with DOX in a standardized procedure.
Keywords: Doxorubicin (DOX); Doxorubicinol (DOXol); UHPLC–MS/MS; Transarterial chemoembolization procedure (TACE); Drug eluting beads; Pharmacokinetics;