Identification of Related Substances in Etimicin Sulfate by HPLC-HRMS/MS / 中国药学杂志

OBJECTIVE: To establish an HPLC-HRMS/MS method for analyzing the structures and sources of the related substances in etimicin sulfate. : The chromatographic separation was achieved on a broad pH range column with a basic elution system composed of[H2O-ammonia-glacial acid(96:3.6:0.4)]-methanol(70:30). Twenty percent of the eluent was detected under positive electrospray ionization(ESI) by Q-Exactive mass spectrometry. The fragmentation pathways were elucidated according to the HRMS and HRMS/MS fragmentation of etimicin and some known compounds. Then the unknown related substances were identified by analyzing their HRMS and HRMS/MS fragmentation with the help of the rule. RESULTS: Sixty-five related substances were detected by the HPLC-HRMS/MS method in the two samples from different companies,among which 38 were detected in the product of company A, 59 in that of company B, and 32 were detected for both companies. Fifty-four related substances were identified or deduced, and the other 11 were not able to be identified due to limited information. Based on the significant difference of impurity spectra between the two enterprises, the key parameters of the synthesis process were analyzed. CONCLUSION: An HPLC-HRMS/MS method, which showes excellent accuracy, is developed to identify the related substances in etimicin sulfate. The resources and structures of the related substances are analyzed, which will be helpful to the process optimization.

A retrospective study on sequential desensitization-rechallenge for antituberculosis drug allergy

BACKGROUND: Antituberculosis (anti-TB) drug allergy often involves multiple concurrently administered drugs which subsequently need to be reinitiated as no better alternatives exist. OBJECTIVE: To describe the results of tailored sequential desensitization-rechallenge (D-R) for anti-TB drug allergy. METHODS: Consecutive patients who had undergone D-R to anti-TB drugs between 1 September 1997 and 31 January 2012 were recruited. Following resolution of the acute reaction, anti-TB drug was restarted at 1:6,000 to 1:3 of the final daily dose (FDD), with gradual single or multiple step daily dose escalation to the FDD. Subsequent drugs were sequentially added ≥3 days later when the preceding drug was tolerated. Full blood count and liver function tests were monitored prior to addition of each new drug. RESULTS: There were 11 patients of whom 10 were male, predominantly Chinese (8 patients). Regimens comprised at least 3 drugs: isoniazid (INH), rifampicin (RIF), ethambutol (EMB), pyrazinamide (PZA), or streptomycin. All patients had nonimmediate reactions, with cutaneous eruptions, where maculopapular exanthema (MPE) was the most common (8 patients). Drug-induced hypersensitivity syndrome (DIHS) occurred in 6 patients, and Stevens Johnson syndrome (SJS) in 2 patients. D-R to INH was successful in 7/9 patients (77.8%) and to RIF/EMB/PZA/streptomycin in all. Of the 2 patients who failed INH D-R, 1 developed fever and MPE on day 3, the other MPE on day 8. D-R with INH and RIF respectively was successful in 2 patients with SJS. Among DIHS patients, 1 failed D-R with INH (fever and MPE on day 3). There were 23/25 (92%) successful D-R among the 11 patients. All patients completed TB treatment of ≥5 months' duration with no cases of drug-resistant TB. CONCLUSION: Tailored sequential TB drug D-R is successful where no better alternative therapies are available, with careful dose escalation and close monitoring, and after a careful risk-benefit assessment.

Recent researches of synthetic mercury sulfide in traditional medicine system / 中国中药杂志

<p><b>OBJECTIVE</b>Herein, the synthesis, component, microstructure and pharmacological and toxicology researches of the Synthetic Mercury Sulfide (S-HgS) a kind of common drug in Chinese, Mongolia, Tibetan medicine, and Indian medicine system were summarized. The similar cognition about mercury toxicity & pharmacological action from some Asian regions was analyzed, and it can supply some useful direction for the traditional Asian medicine system.</p><p><b>METHOD</b>Recent literatures both domestic and abroad were summarized and analyzed.</p><p><b>RESULT</b>S-HgS is the basis of Vermilion, Mongolia-Vermilion, Zuotai, and Ras-sindoor. Athough the processes of synthesis are very different, but the microstructure and pharmacological & toxicology of S-HgS is similar.</p><p><b>CONCLUSION</b>S-HgS has a far-ranging application,and unique curative effect. New technology such as nanotechnology can be used for improving the advancement of traditional Asian medicine.</p>