Structure identification of related substances in doxycycline hyclate by 2D-LC-IT-TOF/MS / 中国药学杂志

OBJECTIVE: To rapidly identify the related substances in doxycycline hyclate tablets and investigate the possible degradation pathways of doxycycline hyclate solution by 2D-LC-IT-TOF/MS. METHODS: Firstly, the chromatography was carried out using the 1stD InertSustain ™C18 (4.6 mm×150 mm, 5 μm) column and a mobile phase containing a mixture of buffer solution (0.25 mol·L-1 ammonium acetate solution-0.1 mol·L-1 ethyldiaminetetraacetic acid disodium; triethyiamine=100:10:1)-acetonitrile (85:15). Solution pH was adjusted to 8.8 with glacial acetic acid. Then a InertSustain C18 (2.1 mm×50 mm, 2 μm) column was used with 0.1% formic acid-water as mobile A and 0.1% formic acid-acetonitrile as mobile B in a gradient elution mode in 2ndD. Electrospray ionization (ESI) source was tested in both positive and negative ion modes. Nebulized gas flow was 1.5 L·min-1. Dry gas flow was 10 L·min-1. The desolvation tube temperature was kept at 200℃. Related substances were characterized according to multi-level MS behaviors. The 2D-LC-IT-TOF/MS method was employed to identify the structures of impurities in forced degradation solutions and illuminate the degradation pathways of doxycycline hyclate solution. RESULTS: A total of eight related substances were detected in doxycycline hyclate tablets. Four of them had a content of more than 0.1%, and their structures were identified to be 4-epidoxycycline, metacycline, β-epidoxycycline and 2-acetyl-2-decar-bamoyldoxycycline. The solution of doxycycline hyclate easily degraded under alkaline condition and generated an open loop compound taken off the keto group. The solution was sensitive to heat, and generated 4-epidoxycycline with a little amount of 4-epi-6-epidoxycycline; but the solution was stable under illumination and acidic condition. CONCLUSION: The established method is suitable for rapid identification of impurities in doxycycline hyclate, which can be applied as a useful analytical tool for quality control and drug process optimization of doxycycline hyclate.

Treatment outcome analysis of CTOP or CHOP regimen in newly diagnosed aggressive non-Hodgkin's lymphoma patients-results of a prospective, open, randomized, multicenter clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the efficacy and toxicity of CTOP and CHOP regimen for newly diagnosed aggressive non-Hodgkin's lymphoma (NHL) patients.</p><p><b>METHOD</b>From Oct 2006 to Jun 2009, 196 patients enrolled into this clinical trial from 72 centers in China were randomized into CTOP or CHOP group.</p><p><b>RESULTS</b>Of 154 patients evaluated, 105 assigned in CTOP group and 49 in CHOP. Complete remission (CR) rate was 73.3%, and response rate (RR) was 87.6% in CTOP group and CR rate 71.4%, RR 86.2% in CHOP group, respectively (both P > 0.05). For B cell lymphomas, there was no difference in outcome between the two groups, but for T cell lymphomas, CR was 71.1% in CHOP, being significantly higher than that of 58.8% in CHOP group. There was no difference in hematological toxicity, GI reaction, liver and kidney function abnormality, but the occurrence of grade 3-4 alopecia in CTOP group (12.4%) was significantly lower than that in CHOP group (40.8%). The progress-free survival and overall survival (PFS and OS) at 1-, 2-, 3-year in CTOP group were 79%, 64.8%, 51.4% and 82.9%, 70.5%, 58.1%respectively; while in CTOP group were 77.6%, 61.2%, 49% and 81.6%, 67.3%, 55.1% respectively.</p><p><b>CONCLUSION</b>CTOP regimen has similar effectiveness to CHOP regimen in newly diagnosed aggressive NHL, but with less side effects, and better efficacy for T cell lymphomas.</p>

Analysis of outocome of pirarubicin-based combination chemotherapy regimen in the treatment of newly diagnosed acute myeloid leukemia-a prospective, open, randomized and multicenter clinical trial / 中华血液学杂志

<p><b>OBJECTIVE</b>To compare the effectiveness and side effects of two chemotherapy regimens [pirarubicin + cytarabine (TA) and daunorubicin + cytarabine (DA)] in patients with acute myeloid leukemia (AML).</p><p><b>METHODS</b>From Oct 2006 to Jul 2009, there were 207 newly diagnosed AML patients randomized into DA or TA group from 72 centers all over the country. The aim of this clinical trial is to observe and evaluate complete remission rate (CR), total remission rate (TRR), and side effect after one or two circles of therapy.</p><p><b>RESULTS</b>In 198 evaluable patients, 126 cases in TA group and 72 in DA group were evalvable, with a ratio of 1.75:1. CR was 69.8% and TRR (CR + PR) was 81.8% in TA group and 63.9%, 80.9% in DA group, correspondingly (P > 0.05). For patients with subtype M(2), CR (77.1%) in TA group was higher than that in DA (60%). There was no difference in side effect between the two groups.</p><p><b>CONCLUSION</b>There is no difference of the effect between TA and DA chemotherapy for newly diagnosed AML patients. But for subtype M(2), TA is more efficacy. And there is no difference in side effect between the two regimens.</p>

Colophony Adsorbing Isolating Herbicidal Substance from Mycotoxin Produced by Pythium aphanidermatum / 微生物学通报

Four kinds of colophony were used to isolate the herbicidal substance from the toxin produced by isolate PAM1 of Pythium aphanidermatum, which had herbicidal activity to Digtaria sanguinealis L and the results showed X-5 was the best one for absorbing herbicidal substance among the four kinds of colophony used. Four solvents including 50% ethanol, 95% ethanol, ethyl acetate and acetone were used as eluting solvent and 2 procedures were tested, and the results of growth inhibition and seed germination indicated that the best eluting procedure was procedure 1.

Electrocardiographic characteristics and radiofrequency catheter ablation results of ventricular tachycardia or premature ventricular contractions originating in the vicinity of atrioventricular annulus / 中华心血管病杂志

<p><b>OBJECTIVE</b>To evaluate the electrocardiographic (ECG) characteristics and results of radiofrequency catheter ablation (RFCA) of idiopathic ventricular tachycardia or premature ventricular contractions (VT/PVCs) originating in the vicinity of atrioventricular annulus.</p><p><b>METHODS</b>Nineteen patients with idiopathic VT/PVCs underwent conventional electrophysiological study and RFCA were included in this analysis. The 12 leads (ECG) characteristics were also analyzed.</p><p><b>RESULTS</b>The VT/PVCs were originated in the vicinity of mitral annulus in 10 cases, including anterolateral (n = 5), posterolateral (n = 3) and posteroseptal (n = 2). The VT/PVCs were originated in the vicinity of tricuspid annulus in the rest 9 cases, including the free wall (n = 5) and the septal portion (n = 4). The 12-lead ECG patterns of VT/PVCs originating in the vicinity of atrioventricular annulus were helpful for determine the site of RFCA. The VT/PVCs were successfully eliminated by RFCA in all cases.</p><p><b>CONCLUSION</b>The exact origin of VT/PVCs originating in the vicinity of atrioventricular annulus could be determined by 12-leads ECG analysis and can be successfully and safely cured by RFCA.</p>

Study on the strategy of Japanese encephalitis immunization using live attenuated vaccine combined with inactivated vaccine / 中华流行病学杂志

<p><b>OBJECTIVE</b>Using the advantages of Japanese encephalitis live attenuated and inactivated vaccine, to reduce the rate of immunization reaction and to increase the effect, we conducted a study on the strategy of immunization in Japanese encephalitis using live attenuated vaccine combined with inactivated vaccine.</p><p><b>METHODS</b>Observing the safety and immune effects of different groups.</p><p><b>RESULTS</b>Data on side effect showed that the rate of moderate and severe systematic reactions of the group who were inoculated with combined vaccine was 0.73%, with local reaction 1.46% while the combined rate of moderate and severe systematic reaction of the group who were inoculated with inactivated vaccine was 2.8%. Under the detection of serum neutralizing antibody, the GMT rose from 1:1.05 - 1:3.35 before vaccination to 1:47.34 - 1:101.30 after vaccination in the different groups. Neutralizing antibody was detected in 97.67% of the combined group. There was a significant difference by comparing neutralizing antibody seroconversion rate of the combined group with the inactivated group (chi(2) = 3.89, P < 0.05), but no significant difference with attenuated group (chi(2) = 0.74, P > 0.05).</p><p><b>CONCLUSION</b>Results showed that in children who previously had been immunized with two doses of inactivated vaccine, the booster administration of live attenuated vaccine was both effective and safe.</p>

The metabolic transformation of (-)-securinine / 药学学报

<p><b>AIM</b>To study the in vitro and in vivo metabolism of (-)-securinine.</p><p><b>METHODS</b>The metabolic transformation of (-)-securinine was studied by using phenobarbital-induced rat liver microsomal incubate containing the NADPH-generating system in vitro and the constitution of the system was optimized. A reversed phase HPLC method was established to analyze the parent drug and its metabolites. The major metabolites were isolated and purified by liquid-liquid extraction, preparative TLC and HPLC, and their structures were elucidated as 6-hydroxyl securinine, 6-carbonyl securinine, 5 beta-hydroxyl securinine and 5 alpha-hydroxyl securinine by 1HNMR, 13CNMR and MS spectral analysis. An HPLC method was developed to analyze securinine and its metabolites in biofluids (bile, urine) of rat. The bile, urine and their enzymatic hydrolyzed samples of the rat i.p. administrated with (-)-securinine were determined by using this method.</p><p><b>RESULTS</b>Four main metabolites of (-)-securinine in rat hepatic microsome incubation were obtained and their structures were elucidated. Metabolites from in vitro study were confirmed in biofluids (bile, urine) which were collected from rats given securinine i.p. It was suggested that 6-hydroxyl securinine was excreted in conjugated form as well by analyzing enzymatic hydrolyzed bile.</p><p><b>CONCLUSION</b>The main metabolic pathway of (-)-securinine in vitro and in vivo is basically elucidated.</p>

Determination of serum granulocyte colony-stimulating factor level in patients with chronic idiopathic neutropenia and its significance / 中国实验血液学杂志

To investigate the serum granulocyte colony-stimulating factor (G-CSF) level in patients with chronic idiopathic neutropenia (CIN) and analyze its clinical significance. By the use of G-CSF-specific enzyme-linked immunosorbent assay (ELISA), the serum levels of G-CSF were determined in 40 cases with chronic CIN, 40 cases with systemic lupus erythematosus (SLE) complicated neutropenia and 40 healthy volunteer (normal control). Results showed that serum G-CSF was positive in 11 normal controls and in 10 cases with SLE, and the G-CSF levels were (27.34 +/- 8.00) ng/L and (26.76 +/- 7.26) ng/L, respectively. Serum G-CSF in 27 cases with CIN was positive, the level was (134.04 +/- 89.29) ng/L, which was higher than that in the normal controls and the cases with SLE (P < 0.01). It was concluded that an obstacle to utilization of G-CSF could be existed in the patients with CIN.