OBJECTIVETo determine the contents of the residual solvents, methanol, ethanol, toluene, dichloromethane and dioxane in ranolazine raw material.

METHODSHeadspace gas chromatography was used to analyze the residual solvents quantitatively. Samples were analyzed on an HP-INNOWAX column with column temperature at 45 degrees Celsius; using water as solvent.

RESULTSFive residual solvents were completely separated. The liner range and recoveries were satisfied. RSD of precision and accuracy was less than 8% with average recoveries between 87.1% and 105.6%.

CONCLUSIONThe method could be used for the quality control of ranolazine raw material.

Acetanilides ; analysis ; Chromatography, Gas ; methods ; Drug Contamination ; prevention & control ; Enzyme Inhibitors ; analysis ; Ethanol ; analysis ; Methanol ; analysis ; Piperazines ; analysis ; Ranolazine ; Reproducibility of Results ; Solvents ; analysis ; Toluene ; analysis

In forensic toxicology analysis, various types of biological samples have their own special characteristics and scope of applications. In this article, the physiological structure of nails, methods for collecting and pre-processing samples, and for analyzing some poisons and drugs in the nails are reviewed with details. This paper introduces the influence factors of drug abuse of the nails. The prospects of its further applications are concluded based on the research results. Nails, as an unconventional bio-sample without general application, show great potential and advantages in forensic toxicology.
Alprazolam/analysis* ; Azabicyclo Compounds/analysis* ; Chromatography, High Pressure Liquid/methods* ; Cocaine/analysis* ; Diazepam/analysis* ; Eszopiclone ; Forensic Toxicology/methods* ; Gas Chromatography-Mass Spectrometry/methods* ; Hair/chemistry* ; Humans ; Illicit Drugs/analysis* ; Nails/physiology* ; Piperazines/analysis* ; Specimen Handling/methods* ; Substance Abuse Detection/methods*

AIMTo analyse the main impurity of caderofloxacin.

METHODSThe impurity of caderofloxacin was analysed and determinated by RP-HPLC/ESI/MS with a Zorbax SB-C18 (150 mm x 4.6 mm ID, 5 microns) column. The mobile phase was acetonitrile-0.5% acetic acid solution (17:83). A compound was synthesized: 1-cyclopropyl-8-(difluoromethoxy)-6-fluoro-1, 4-dihydro-7-(1-piperazinyl)-4-oxo-3-quinoline carboxylic acid (DMCA). Its HPLC chromatogram, UV and MS spectrum were compared with those of the impurity in caderofloxacin.

RESULTSThe molecular weight of the impurity was 14 less than that of caderofloxacin. It means the impurity was a CH2-group less than caderoflixacin. The tR, UV and MS of DMCA were the same as those of the impurity in caderofloxacin.

CONCLUSIONBased on the tR (HPLC), UV and MS, the impurity of caderofloxacin is confirmed as DMCA.

Anti-Infective Agents ; chemistry ; Carboxylic Acids ; analysis ; chemistry ; Chromatography, High Pressure Liquid ; methods ; Drug Contamination ; Fluoroquinolones ; chemistry ; Molecular Structure ; Piperazines ; chemistry ; Quinolines ; analysis ; chemistry ; Spectrometry, Mass, Electrospray Ionization

PURPOSE: The aim of this study was to investigate the influence of body mass index (BMI) on the level of peak luteinizing hormone (LH) after gonadotropin-releasing hormone (GnRH) stimulation in girls with central precocious puberty (CPP) and advanced puberty (AP). METHODS: This study conducted a retrospective review of the medical records of 113 girls (7 to 9 years old; 24 CPP, 89 AP) who underwent a GnRH stimulation test. The following parameters were evaluated: chronologic age (CA), bone age (BA), the difference between BA and CA (BA-CA), height, weight, BMI, and the levels of basal LH, peak LH, basal follicle stimulating hormone (FSH), peak FSH, and basal estradiol. RESULTS: The peak LH level was negatively correlated with weight-standard deviation score (SDS) and BMI-SDS; furthermore, the peak LH level was positively correlated with both basal and peak FSH levels. Using multivariate analysis, BMI-SDS was found to be a significant factor in predicting peak LH levels after GnRH administration. When the subjects were divided into four groups by quartile of peak LH level, the mean BMI-SDS of the highest LH group was significantly lower than the mean BMI-SDS of the lowest LH group. CONCLUSION: LH levels rise after GnRH administration is blunted in precocious and advanced pubertal girls with high BMI. The impact of BMI on the GnRH stimulation test should be considered when evaluating sexual precocity in girls.
Body Mass Index ; Follicle Stimulating Hormone ; Gonadotropin-Releasing Hormone ; Lutein ; Luteinizing Hormone ; Medical Records ; Multivariate Analysis ; Piperazines ; Puberty ; Puberty, Precocious ; Retrospective Studies

PURPOSE: In spite of its safety and fesibility, it is not completely certain whether two-port laparoscopic cholecystectomy can be applied for the same indications as four-port cholecystectomy. METHODS: We retrospectively analyzed the prospectively collected data of the patients who had undergone either two-port or four-port laparoscopic cholecystectomy at the Department of Surgery, Daejeon St. Mary's Hospital between March 2007 and August 2009. A total of 341 patients were included. For our two-port cholecystectomy, combining a transumbilical wound retractor with a surgical glove on which there was a 11 mm trocar and two pipes were attached comprised an umbilical common channel, and another port was inserted through the epigastrium. The overall procedure was similar to four-port laparoscopic cholecystectomy. RESULTS: The patients were classified into the four-port group (n=261) and the two-port group (n=80) according to the operative method. All the two-port cholecystectomies were followed by four-port procedures. The operative indications for these two procedures were identical. No significant difference was observed for the mean operation time, the conversion rate, the postoperative hospital stay and the complications between each group. Multivariate analysis revealed that the factors making two-port surgery longer than the 75 percentile of the overall operation time were the development of intraoperative complications (RR 14.3; p=0.005; C.I. 2.255-90.853), a operation for the patients who visited the emergency room (RR 10.4; p=0.012; C.I. 1.684-63.798), open conversion or making additional port(s) (RR 9.9; p=0.032; C.I. 1.219-80.958) and a body-mass index greater than 25 (RR 5.5; p=0.025; C.I. 1.244-24.731). CONCLUSION: This study documents that our two-port laparoscopic cholecystectomy seems to have the potential to replace the conventional four-port laparoscopic cholecystectomy.
Alkanesulfonic Acids ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Emergencies ; Gloves, Surgical ; Humans ; Intraoperative Complications ; Length of Stay ; Multivariate Analysis ; Piperazines ; Prospective Studies ; Retrospective Studies ; Surgical Instruments

PURPOSE: In spite of its safety and fesibility, it is not completely certain whether two-port laparoscopic cholecystectomy can be applied for the same indications as four-port cholecystectomy. METHODS: We retrospectively analyzed the prospectively collected data of the patients who had undergone either two-port or four-port laparoscopic cholecystectomy at the Department of Surgery, Daejeon St. Mary's Hospital between March 2007 and August 2009. A total of 341 patients were included. For our two-port cholecystectomy, combining a transumbilical wound retractor with a surgical glove on which there was a 11 mm trocar and two pipes were attached comprised an umbilical common channel, and another port was inserted through the epigastrium. The overall procedure was similar to four-port laparoscopic cholecystectomy. RESULTS: The patients were classified into the four-port group (n=261) and the two-port group (n=80) according to the operative method. All the two-port cholecystectomies were followed by four-port procedures. The operative indications for these two procedures were identical. No significant difference was observed for the mean operation time, the conversion rate, the postoperative hospital stay and the complications between each group. Multivariate analysis revealed that the factors making two-port surgery longer than the 75 percentile of the overall operation time were the development of intraoperative complications (RR 14.3; p=0.005; C.I. 2.255-90.853), a operation for the patients who visited the emergency room (RR 10.4; p=0.012; C.I. 1.684-63.798), open conversion or making additional port(s) (RR 9.9; p=0.032; C.I. 1.219-80.958) and a body-mass index greater than 25 (RR 5.5; p=0.025; C.I. 1.244-24.731). CONCLUSION: This study documents that our two-port laparoscopic cholecystectomy seems to have the potential to replace the conventional four-port laparoscopic cholecystectomy.
Alkanesulfonic Acids ; Cholecystectomy ; Cholecystectomy, Laparoscopic ; Emergencies ; Gloves, Surgical ; Humans ; Intraoperative Complications ; Length of Stay ; Multivariate Analysis ; Piperazines ; Prospective Studies ; Retrospective Studies ; Surgical Instruments

The drugs such as sildenafil adulterated in herbal products and dietary supplements may endanger human health. The number of the new modified derivatives is increasing recently. Based on Q-TOF-MS, a new sildenafil analogue was found. It was isolated and purified by preparative liquid chromatography. Its structure was determined by NMR, as 1-[4-propoxy-3-(6, 7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo[4, 3-d] pyrimidin-5-yl)phenylsulfonyl]-4-methylpiperazine. Compared with sildenafil, the ethoxy group of the benzene ring moiety was moved to the propoxy group, which had not been reported in China. The mass spectrometric behavior pattern of the structure type was summarized, which can greatly accelerate the structural analysis of novel analogues.
Chromatography, High Pressure Liquid ; Dietary Supplements ; analysis ; Drug Contamination ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Piperazines ; chemistry ; isolation & purification ; Sildenafil Citrate ; chemistry ; Spectrometry, Mass, Electrospray Ionization

The effects of monoterpene perilly alcohol (POH) alone or in combination with STI571 on the proliferation and apoptosis of the cell line K562 positive for Bcr/Abl were investigated. By using cell culture, the effect of the drugs on the proliferation of the cells was studied. TUNEL and flow cytometry assay of FITC-Annexin V and PI labeled cells were applied to detect the effects of the drugs on the apoptosis of the cells. The results showed that at 36 h, IC50 of POH on K562 positive for Bcr/Abl and HL-60 negative for Bcr/Abl were 81.0 +/- 11.3 micromol/L and 113.6 +/- 23.4 micromol/L respectively (P>0.05). POH could inhibit the proliferation of K562 in a time- and dose-dependent manner with the inhibitory rate of 100 micromol/L POH on K562 cells at 36 h being (53.2 +/- 3.65)%. K562 cells were more sensitive to STI571 than POH. IC50 of STI571 on K562 cells in 36 h was (0.256 +/- 0.054) micromol/L. In a time- and dose-dependent manner, POH induced the apoptosis of K562 cells with the percentage of apoptotic cells by 100 micromol/L POH at 40 h being (21.0 +/- 3.3)%. Both 100 micromo/L POH and 0.2 micromol/L STI571 had the same inhibitory effects on the K562 cells at 36 h. But at 12 and 24 h, the inhibitory rate of POH was significantly higher than that of STI571 (P<0.05) and the ability of STI571 inducing apoptosis at 36 h was greater than that of POH. 50 micromol/L, 100 micromol/L and 200 micromol/L POH in combination with 0.2 micromol/L STI571 could obviously increase the inhibitory effects on the cellular proliferation. Combined use of 50 micromol/L, 100 micromol/L, 200 micromol/L with 0.2 micromol/L STI571 could strongly induced apoptosis, especially 200 micromol/L POH in combination with 0.2 micromol/L STI571. It was concluded that the antileukemia effect of POH had no obvious Bcr/Abl positive selectivity. POH can inhibit the proliferation of K562 and induce the apoptosis in a time- and dose-dependent manner. K562 cells were more sensitive to STI571 than POH. POH in combination with STI571 could obviously enhance the abilities of STI571 inhibiting the proliferation and inducing apoptosis of K562 cells.
Antineoplastic Agents/*pharmacology ; Apoptosis/*drug effects ; Dose-Response Relationship, Drug ; Drug Synergism ; Fusion Proteins, bcr-abl/analysis ; HL-60 Cells ; K562 Cells ; Monoterpenes/*pharmacology ; Piperazines/pharmacology ; Pyrimidines/*pharmacology

A 63-year-old man was found in the street after overrun by a car. Postmortem CT revealed multiple bone fractures, but surprisingly all without any relevant hemorrhage which would have been expected under such circumstances. A round radiopaque formation was found in the duodenum, which was reminiscent of ingested tablets. The toxicological analysis revealed high concentrations of zopiclone and alcohol. By combining radiologic and forensic results, zopiclone and alcohol intoxication were concluded as the cause of death, followed by a postmortem overrun accident.
Accidents, Traffic ; Alcoholic Intoxication/*diagnosis ; Azabicyclo Compounds/analysis/*poisoning ; Duodenum/*radiography ; Fatal Outcome ; Humans ; Hypnotics and Sedatives/analysis/*poisoning ; Male ; Middle Aged ; Piperazines/analysis/*poisoning ; Tomography, X-Ray Computed/*methods

To produce leukemic STI571-resistant cell lines and to explore the molecular mechanism of STI571-resistance, cell lines K562-n and K562-n/VCR were induced by exposing cells to gradually increasing STI571 concentration of culture medium to have STI571-resistance and major biological characteristics between these subclones and the parent cells were compared. The results showed that a STI571-resistant cell line based on multidrug-resistance was established, which exhibited 23.41-fold resistance to STI571, 662.26-fold resistance to VCR and cross-resistance to HHT. K562-n/STI was generated from K562-n and had some characteristics of MDR. The intracellular accumulation of DNR in K562-n/STI and K562-n/VCR/STI were 33.24 and 18.76 respectively. Transcription of mdr-1 gene in both K562-n/STI and K562-n/VCR/STI was positive. Cell doubling time of K562-n/STI and K562-n/VCR/STI was significantly longer than that in their parent cells (P <0.05). And proliferation index was also higher than that in parent cells (P <0.05). It is conclusion that the tolerance of K562-n cells to STI571 can be augmented by adding low-dose of STI571 into the culture medium repeatedly. K562-n/STIs expressed MDR at some extent, and transcription of mdr-1 gene in K562-n/STIs was positive. As K562-n is a cell line used to develop human leukemia in nude mice, K562-n/STI and K562-n/VCR/STI 571 will contribute to the study of mechanism of STI571-resistance as in vitro and in vivo experimental models.
Antineoplastic Agents ; pharmacology ; Benzamides ; Cell Cycle ; drug effects ; Cell Proliferation ; drug effects ; Drug Resistance, Neoplasm ; Genes, MDR ; Humans ; Imatinib Mesylate ; K562 Cells ; Piperazines ; pharmacology ; Pyrimidines ; pharmacology ; RNA, Messenger ; analysis