With the advance of drug development and research techniques, the drug metabolic processes and mechanism can be more deeply achieved. As the drug metabolism and pharmacokinetics process are mediated by drug metabolizing enzymes and transporters, study of drug metabolizing enzymes and transporters has become an important part for drug development. The traditional immunoassays with low sensitivity and poor specificity can not reflect the accurate expression level of drug metabolizing enzymes and transporters. We now give a brief review on the quantitative study of drug metabolizing enzymes and transporters by mass spectrometry-based proteomic approach.
Enzymes ; chemistry ; Humans ; Inactivation, Metabolic ; Mass Spectrometry ; Membrane Transport Proteins ; chemistry ; Pharmacokinetics ; Proteomics

The fragmentation pathways of two taxanes drugs have been studied in positive ion mode by Q-TOF with the advantages of high mass accuracy and high resolution analysis. The [M+H] + ions were observed by ESI-MS, from which the molecular weights were obtained. Using the protonated pseudo-molecular ions [M+H]+ as internal reference compounds, the accurate mass and element composition of the fragment ions were determined. The collision induced dissociation (CID) data of the [M+H] ions provided fragmentation pathways of related compounds. Results showed that the major cleavage pathways of paclitaxel and docetaxel were the same that the cleavage of C-O bond between the side chain and taxol skeleton easily occurred, then stripping of the functional groups on the parent ring. Some common fragments were formed, such as m/z 105.033 7, 291.137 3, 309.148 5, 327.159 7, 387.181 2 and 509.217 4, which would provide a basis for future qualitative and quantitative analysis of taxanes in vitro and in vivo.
Paclitaxel ; chemistry ; Peptide Fragments ; chemistry ; Spectrometry, Mass, Electrospray Ionization ; methods ; Taxoids ; chemistry

The fragmentation pathways of five estrogens (estradiol, estrone, equilin sulfate, 17 a-dihydroequilin sulfate and equilenin sulfate) have been studied with high resolution and high mass accuracy using electrospray ionization quadrupole time-of-flight mass spectrometry (ESI-Q-TOF/MS) in the negative ion mode. Molecular weights were obtained from [M-H](-) ions in the product ion spectra. The results indicate that the five structurally similar estrogens have similar fragmentation pathways. Using their stable isotope forms as internal reference compounds, the accurate mass and composition of the fragment ions were determined. During collision-induced dissociation (CID), cleavage is initiated by loss of oxygen atoms from carbon-17, after which D and C rings cleave sequentially and rearrange to finally form stable conjugate structures with highly abundant characteristic fragment ions at m/z 183 (accompanied by m/z 181), m/z 169 and m/z 145 (accompanied by m/z 143). Understanding these characteristic fragmentation pathways of estrogens will be helpful in identifying the structures of steroid hormones in general.
Chemical Fractionation ; methods ; Equilenin ; chemistry ; Equilin ; analogs & derivatives ; chemistry ; Estradiol ; chemistry ; Estrogens ; chemistry ; Estrone ; chemistry ; Ions ; Spectrometry, Mass, Electrospray Ionization

The paper is aimed to provide a novel index, named as multidimensional spatial triangular area, for the evaluation of the release-absorption correlation of multiple component traditional Chinese medicines (TCMs). The applicability of the method was demonstrated by the example data. The method and standard practice for evaluation of the release-absorption correlation for western medicines with single compound could not be applied to TCMs with multiple components. The release percentage or absorption percentage of the multiple components for TCMs at the sampling time was a point in the multidimensional space. The area of the triangle formed byt the sequential three points represented the changing characteristics of the components' release and absorption kinetics. The side lengths of the triangle could be calculated from the spatial distances between each two of the sequential three points. Then the triangle area could be obtained by the side lengths. The in vitro release-in vivo absorption correlation of the multiple components could be represented by the correlation between the integrating values of the release triangle areas and that of the absorption triangle areas. The results of the examples indicated that the multidimensional spatial triangular area method could treat the multiple components in a holistic way, in line with the holism the hi he TCMs. Therefore, the multidimensional spatial triangular area method provided new methodology for the release-absorption correlation of the TCMs with multiple components.
Algorithms ; Chemistry Techniques, Analytical ; Drug Combinations ; Drugs, Chinese Herbal ; analysis ; isolation & purification ; pharmacokinetics ; Medicine, Chinese Traditional ; Plants, Medicinal ; chemistry

OBJECTIVETo compare the differences in intrapulmonary shunt (Qs/Qt) and arterial oxygenation between selective left lower lobar blockade by Coopdech endobronchial blocker tubes (BB) and one lung ventilation (OLV) by left-sided double-lumen endobronchial tubes (DLT) in patients with normal pulmonary function.

METHODSThirty-six patients (aged 32-64 years) scheduled for lower esophageal surgery were allocated randomly into BB and DLT groups (n=18). Anesthesia was induced and maintained with Propofol by target controlled infusion with intravenous administration of sufentanil and cisatracurium if needed. A 35 to 39 French tube was placed in the DLT group, and an 8.0-mm (internal diameter) single-lumen endotracheal tube was used in the BB group where a 9 French Coopdech BB was advanced into the left lower lobar bronchus guided by a fiberoptic bronchoscope. The variables recorded were blood gas analysis data from the venous and arterial blood samples at 20 min after two-lung ventilation in supine position (T(1)), 20 min after initiation of one-lung ventilation or selective left lower lobar blockade by inflating BB balloons in the right lateral decubitus position (T(2)), total collapse of the left lung or the left lower lobe after the pleura was opened (T(3)), and before tracheal extubation (T(4)). Qs/Qt was calculated using a standard formula based on the three-compartment model. Upon pleura opening, the effectiveness of lung collapse was evaluated by the surgeon who performed the surgery. Chest radiograph and arterial blood gas analyses were performed the day after the operation.

RESULTSBoth of the groups were similar with regard to rank of the surgical exposure, pH, PaCO(2), hemoglobin from T(1) to T(4), Qs/Qt, PaO(2), PO(2), and oxygenation index at T1. In BB group, a significant reduction of Qs/Qt and greater improvements in PaO(2), PO(2), oxygenation index at T(2), T(3) and T(4) were observed in comparison with those in DLT group (P<0.05 or <0.01). No lobe collapse was observed postoperatively in BB group, but 2 patients in DLT group showed left lower lobe atelectasis. The patients in BB group showed better postoperative arterial oxygenation and shorter postoperative hospital stay (P<0.01).

CONCLUSIONSelective left lower lobar blockade by Coopdech endobronchial blocker tube during lower esophageal surgery provides a lower intraoperative intrapulmonary shunt and a better intra- and postoperative arterial oxygenation..

Adult ; Blood Gas Analysis ; Bronchoscopes ; Continuous Positive Airway Pressure ; instrumentation ; methods ; Esophageal Neoplasms ; surgery ; Female ; Fiber Optic Technology ; Humans ; Intubation, Intratracheal ; methods ; Lung ; physiology ; Male ; Middle Aged ; Oxygen ; administration & dosage ; blood ; pharmacology ; Pulmonary Ventilation ; Thoracic Surgical Procedures ; methods

AIMTo isolate and identify a glucuronide metabolite of SFZ-47 [3H-1,2-dihydro-2-(4-methyl-phenylamino)methyl-1-pyrrolizinone], which is difficult to synthesize because it undergoes hydrolysis and intramolecular acyl migration at physiological pH, in rabbit urine.

METHODSTwo rabbits were ig 200 mg doses of SFZ-47. Urine was collected for 24 h, adjusted to pH 4.0 with acetic acid and lyophilized. The residues were reconstituted in 25 mL methanol and centrifuged at 5,000 r.min-1 for 10 min. The supernatant was filtered (0.45 micron) and then isolated with semi-preparative reversed phase HPLC. The eluent collected from individual peaks was evaporated by rotary evaporation and freeze-drying. Compounds were then identified with electrospray ion trap mass spectrometry and 1HNMR spectroscopy.

RESULTSThe 1HNMR and ESI-MSn results indicate that the metabolite is the 1-O-acyl beta-D-glucuronide conjugate of 4-(3H-1,2-dihydro-1-pyrrolizinone-2-methylamino) benzoic acid.

CONCLUSIONThis method was shown to be rapid and simple and gave excellent resolution from endogenous constituents in urine, and it is suitable for preparation of the glucuronide metabolites of SFZ-47 and its analogues.

Animals ; Anti-Inflammatory Agents, Non-Steroidal ; metabolism ; urine ; Chromatography, High Pressure Liquid ; Male ; Molecular Structure ; Pyrroles ; chemistry ; metabolism ; urine ; Rabbits ; Spectrometry, Mass, Electrospray Ionization

AIMTo investigate the fragmentation behavior of triazolobenzodiazepines and to develop a specific, sensitive and rapid LC/MSn assay for simultaneous determination of estazolam, alprazolam and triazolam in human urine.

METHODSAfter oral administration of a single 4 mg dose of the drugs to each of three healthy volunteers, urine samples were purified by solid-phase extraction, and then injected into an ODS column (150 mm x 4.6 mm) with a mobile phase of methanol-water (8:2) for LC/MSn analysis. The structures of estazolam, alprazolam and triazolam in human urine were identified by direct comparison of the observed mass spectra and the chromatographic retention time with those of the reference substance. The mass spectrometer (Finnigan LCQ) was operated in positive mode and in two scan modes including SIM and full scan MS/MS mode. The obtained mass spectra was analyzed assisted with the software Mass Frontier 1.0 for their fragmentation pathways.

RESULTSThe full scan MS/MS spectra of each compound gave characteristic fragment ions of [M + H - N2]+ and [M + H - Cl]+. The detection limit was below 0.5 ng.mL-1 for estazolam, alprazolam and triazolam in human urine.

CONCLUSIONThe method is useful in forensic and clinical toxicology in which unequivocal identification of eatazolam, alprazolam and triazolam is desired.

Alprazolam ; urine ; Anti-Anxiety Agents ; urine ; Chromatography, Liquid ; Estazolam ; urine ; Humans ; Male ; Spectrometry, Mass, Electrospray Ionization ; Triazolam ; urine

The bevacizumab and its glycoforms were analyzed by matrix-assisted laser desorption ionization-time of flight-time of flight-mass spectrometry (MALDI-TOF-MS), sodium dodecyl sulfate polyacrylamide gel electrophoresis ( SDS-PAGE) and short-gun strategy, with the sequence of unique peptide and seventeen glycoforms being characterized. The bevacizumab and its glycopeptides concentrations in mice plasma with different intravenous injection doses of bevacizumab were detected and the concentration-time curves were obtained by parallel reaction monitoring ( PRM) method based on liquid chromatography-tandem mass spectrometry (LC-MS / MS) technique. First, standard curves were created for quantification of mAb in mice plasma, which showed good linearity, with the correlation coefficient (R2 ) value of 0. 998 and the lower limit of quantification of 66 fmol. Detection results of high and low doses of the drug in the mice plasma samples showed that the drug concentration-time curve trend was consistent, e. g. the concentration was decreasing. However, the results of quantitation of seventeen glycoforms demonstrated that the metabolism of different glycoforms was different. The concentrations of most glycoforms increased first, whereas the metabolism afterwards differed by different glycoforms.

OBJECTIVETo evaluate and analyze the mechanism of Pizhen for the treatment of patients with scapular muscle fasciitis.

METHODSOne hundred and sixteen patients were divided into two groups according to random number table method, 58 cases in the treatment group and 58 cases in the control group. After treatment, 109 patients were followed up, and 7 patients lost follow-up (2 cases in the treatment group and 5 patients in the control group). In the treatment group, there were 15 males and 41 females, with a mean age of (28.02 +/- 4.85) years; the course of disease ranged from 0.25 to 3 years; and the patients were treated by Pizhen once a week,and 2 weeks were one treatment course. In the control group, there were 19 males and 34 females, with a mean age of (27.23 +/- 4.54) years old; the course of disease ranged from 0.25 to 1 year; and the patients were treated by acupuncture massage instrument, 20 minutes at a time,once a day for 2 weeks. Soft tissue displacement and banana area were tested by a soft tissue tension tester, pressure value was measured by pressure measuring instrument, and VAS was recorded by pain visual analog scale record.

RESULTSThere were significant differences in tissue displacement, banana area, pressure value and VAS between two groups before and after treatment. The tissue displacement and pressure value in the treatment group were higher than those in the control group,while banana area and VAS were lower than those in the control group. In the treatment group, 30 patients healed, 13 patients got marked improvement, 12 good and 1 poor;while 16 patients healed, 19 patients got marked improvement,11 good and 7 poor in the control group. The therapeutic effects in the treatment group was better than that in the control group.

CONCLUSIONPizhen is an effective method to treat pain in patients with scapular muscle fasciitis by relaxing tendon of soft tissue around pain point of scapular and relaxing compress and stimulation of nerves.

Acupuncture Points ; Acupuncture Therapy ; instrumentation ; Adult ; Case-Control Studies ; Fasciitis ; therapy ; Female ; Humans ; Male ; Treatment Outcome ; Young Adult

Due to the diversity of components within the traditional Chinese medicines (TCMs), the release profiles of the components in the TCM dosage forms vary dramatically and no quantification method is available to determine the variance yet. Based upon the principles of Kalman filter method, the authors defined a new parameter, relative chemomic error (epsilon), to evaluate the asynchronous nature of the components in TCMs, and a derivative parameter as synchronization factor (SF) to quantify the synchronicity of the chemome of the TCMs. The average synchronization factor (SF(av)) was accordingly derived to simultaneously quantify the release/dissolution profiles of the multi-components in TCMs. Randomly generated simulation data were processed to demonstrate the chemomic data processing and the methodology. The results indicated that the novel parameter epsilon was well correlated (r = 0.996 8) with the coefficient of variation from the conventional release profiles of all the components. As the asynchronicity was the intrinsic characteristics of the multi-component TCMs, the synchronicity might be a new target of quality control of TCMs. The methods established by this report can be used a quantitative tool for the evaluation of the chemomic release synchronization of TCMs.
Algorithms ; Chemistry Techniques, Analytical ; Drug Combinations ; Drugs, Chinese Herbal ; analysis ; chemistry ; Evaluation Studies as Topic ; Medicine, Chinese Traditional