Selective separation, detection of zotepine and mass spectral characterization of degradants by LC-MS/MS/QTOF / 药物分析学报

A simple, precise, accurate stability-indicating gradient reversed-phase high-performance liquid chromatographic (RP-HPLC) method was developed for the quantitative determination of zotepine (ZTP) in bulk and pharmaceutical dosage forms in the presence of its degradation products (DPs). The method was developed using Phenomenex C18 column (250 mm ~ 4.6 mm i.d., 5 mm) with a mobile phase containing a gradient mixture of solvents, A (0.05%trifluoroacetic acid (TFA), pH ? 3.0) and B (acetonitrile). The eluted compounds were monitored at 254 nm;the run time was within 20.0 min, in which ZTP and its DPs were well separated, with a resolution of 41.5. The stress testing of ZTP was carried out under acidic, alkaline, neutral hydrolysis, oxidative, photolytic and thermal stress conditions. ZTP was found to degrade significantly in acidic, photolytic, thermal and oxidative stress conditions and remain stable in basic and neutral conditions. The developed method was validated with respect to specificity, linearity, limit of detection, limit of quantification, accuracy, precision and robustness as per ICH guidelines. This method was also suitable for the assay determination of ZTP in pharmaceutical dosage forms. The DPs were characterized by LC-MS/MS and their fragmentation pathways were proposed.

Hepatoblastoma: Experience from a single center.

Background: The cornerstones of successful treatment of hepatoblastoma (HB) include preoperative chemotherapy followed by complete anatomical resection of tumor, followed by chemotherapy. Advances in chemotherapy in the last 2 decades have been associated with a higher rate of tumor response and possibly a greater potential for resectability. Aims: We analyzed our single center experience with neoadjuvant chemotherapy (NACT) and surgery in HBs. Settings and Design: Our study included all children with HBs who received NACT and underwent surgical excision from January 1997 to July 2004. Materials and Methods: Patient characteristics, clinical features, clinical course, treatment modalities, and long-term outcome were analyzed. Results: There were 9 boys and 3 girls, aged 5-60 months (median age at tumor diagnosis was 24 months). All received NACT containing cisplatin and doxorubicin. Of the 12 children, 9 underwent hepatectomy and among them, 4 patients each had right and left hepatectomy and 1 patient underwent right extended hepatectomy. After surgery, all patients completed rest of the chemotherapy course (total 6 cycles). R0 resection was carried out in all the 9 cases with no life-threatening complications. Conclusions: Our experience of the 9 cases, although less in number, reaffirms the advantages of NACT followed by surgery. The prognosis for patients with resectable tumors is fairly good in combination with chemotherapy.

R659X mutation in the MLH1 gene in hereditary non-polyposis colorectal cancer (HNPCC) in an Indian extended family.

Background & objective: Hereditary non-polyposis colorectal cancer (HNPCC or Lynch syndrome), is a genetically heterogeneous disorder that is believed to account for 2–10 per cent of all the colorectal cancer cases. The disease follows autosomal dominant inheritance pattern with high penetrance (85%) and younger age of onset when compared to patients with sporadic tumours. HNPCC is associated with germ-line mutations in the DNA mismatch repair (MMR) genes namely MLH1, MSH2, MSH6, and PMS2. The present study was aimed at analyzing mismatch repair gene(s) in an extended Indian family satisfying the Amsterdam criteria, and extending the analysis to general population to estimate frequency of the mutations/polymorphisms observed. Methods: A total 12 members of the HNPCC family were studied for genetic investigation. Ethnically matched 250 normal individuals were also included as controls to study the observed mutations/ polymorphisms at population level. Results: The analysis resulted in identification of a 1975C>T mutation in exon 17, resulting in substitution of arginine residue with stop codon at codon 659. 655A>G substitution was also observed, resulting in replacement of isoleucine with valine at codon 219. Similar analysis on 250 ethnically matched control subjects revealed complete absence of R659X mutation, while I219V variant was found in 9.8 per cent of the controls. Interpretation & conclusion: R659X mutation correlates with disease phenotype, and 655A>G locus is highly polymorphic. Our study suggested that R659X substitution was prime cause for the disease phenotype in this family. I219V substitution is a polymorphism having no association with the disease onset or segregation. The family members harbouring this mutation were advised to be under regular medical surveillance.

Surfactant modified coir pith, an agricultural solid waste as adsorbent for phosphate removal and fertilizer carrier to control phosphate release.

The surface of coir pith, an agricultural solid waste was modified using a cationic surfactant, hexadecyltrimethylammonium bromide (HDTMA) and the modified coir pith was investigated to assess the capacity for the removal of phosphate from aqueous solution. Optimum pH for maximum phosphate adsorption was found to be 4.0. Langmuir and Freundlich isotherms were used to model the adsorption equilibrium data. Kinetic studies showed that the adsorption obeyed second order kinetics. Thermodynamic parameters were evaluated and the overall adsorption process was spontaneous and endothermic. Effect of coexisting anions has also been studied. The feasibility of using spent adsorbent as fertilizer carrier to control phosphate release was also investigated.

Atlantoaxial dislocation associated with the maldevelopment of the posterior neural arch of axis causing compressive myelopathy.

The craniovertebral junction has a predilection for a variety of congenital anomalies due to its complex development. The association of atlantoaxial dislocation (AAD) with the maldevelopment of the posterior arch of axis is extremely rare. We report two such cases and present the management strategy.

Torture and a doctor.

Modern media today emphasize about on going humanitarian & human rights disasters. The latest torture these days is characterized by adopting technological sophistication that leaves behind few physical traces. Nonetheless, agencies such as Amnesty International have provided convincing proof of applying torture in many countries. ‘The Lancet’ highlights evidence that doctors, physician assistants, nurses, medics at Abu Gharaib assisted in or remained silent in the face of prisoner abuse. Lieutenant Colonel Joe Richard, a spokesman for the Pentagon criticized the Lancet article as a “broad – brushed indictment” based on “allegations” [1]. But if the Medical faculty is able to document the victims in a fair manner they can come out of these allegations. This article is a miniscule contribution to the medical faculty to inculcate awareness about the degrading, inhumane act(s) and how one can go about to curb or eradicate the same.

Percutaneous transluminal angioplasty with cutting balloon and stenting for isolated bilateral aorto-coronary ostial stenosis in a young female.

Coronary artery disease involving both coronary ostia (left main and right coronary) is extremely rare in a premenopausal female, without pre-existing coronary risk factors. We report a case of tight bilateral coronary ostial disease which presented in unusual clinical circumstances in a young female, which was successfully revascularized by single-stage aorto-ostial cutting balloon angioplasty and stenting.

Preceding infection as a risk factor of stroke in the young.

INTRODUCTION: The cause of stroke in the young remains unknown in 20-50% of the patients. Infections preceding stroke have been recently recognised to be an independent risk factor of stroke. MATERIAL AND METHODS: Sixty consecutive patients aged 40 years or less presenting with ischaemic completed stroke are taken up for the study. Patients with neurological deficit of less than 24 hours, evidence of haemorrhage on CT scan, infection occurring after the onset of stroke were excluded. Controls consisted of age and sex matched persons residing in the same area. Both the groups were enquired about preceding fever and infections and were examined for evidence of infections. Serum was examined for antibodies against measles, herpes simplex, and Japanese B encephalitis viruses. Cultures were put up from appropriate samples and CSF examined in patients only. RESULTS: Evidence of infection was noted in 26 (43.3%) of patients and 6 controls (p < 0.001). History of fever was elicited in 23 patients and 3 controls while 15 patients were febrile on examination at admission. Signs of local infection was observed in 14 patients and one control. The commonest site of infection was respiratory tract. Cultures were positive in 11 patients, commonest being beta haemolytic streptococci in six from throat. Conventional risk factors were identical in both groups of patients with and without evidence of preceding infection. Smoking and alcoholism were significantly higher in patients with preceding infection. CONCLUSION: Preceding infection is an important risk factor of stroke in the young. Smoking and alcoholism are more frequent in patients with preceding infection. Whether they predispose the individual for infection or infection increases the stroke risk in them needs to be examined.

Inhibitory effect of Garcinia kola on lipid peroxidation in rat liver homogenate.

Garcinia kola, (a herb grown in Nigeria; calorific value 358.54 k.cal/100 g) inhibited in vitro lipid peroxidation of rat liver homogenate in a dose dependent manner. The inhibitory activity of G.kola was not affected by heating (100 degrees C/10 min). The antioxidant component of G.kola was soluble in aqueous and ethanolic media. The active component(s) in G. kola responsible for its inhibitory activity on lipid peroxidation is tentatively identified as isoflavones.

Dapsone syndrome--a five year retrospective analysis.

Seventeen cases of dapsone syndrome were seen in five years from 1992 onwards. Their mean age was 27.8 years (range 11 to 60 years). Male to female ratio was 1.1:1. Of these cases, seven had confirmed leprosy, nine were cases of suspected leprosy and one case had lichen planus. On an average, they developed the symptoms 27 days after the intake of dapsone. The cutaneous lesions were in the form of erythematous papules and plaques (13 cases), eczematous lesions (four cases) and associated bullous lesions (two cases). The other manifestations were: fever (16 cases), pruritus (15 cases), lymphadenopathy (14 cases), hepatomegaly (10 cases), icterus and oral erosions (five cases each), photosensitivity (four cases) and splenomegaly (two cases). Previous drug allergy was present in four cases. Elevated ESR and liver enzyme levels were invariable findings. Raised bilirubin levels and hemolytic anaemia were seen in eight cases. Apart from one case with hepatic encephalopathy, all other cases had a favourable outcome either on conservative management (eight cases) or on oral corticosteroids (eight cases). Oral provocation test was done in two cases with positive response while intradermal test was not very reliable.

EEG spectral power reduction and learning disability in rats exposed to lead through postnatal developing age.

The present study was carried out to assess electrophysiological and behavioral changes in Wistar rats caused by consuming a daily dose of lead acetate (400 micrograms lead/g body weight/day, given by gastric intubation, from second day of birth to 60 days of age. At 60 days of age, the lead treated rats showed in both wakeful and slow wave sleep stages, a statistically significant reduction in the delta, theta, alpha and beta band EEG spectral power in motor cortex (MC) and hippocampus (HI) with the exception of the delta and beta bands power of MC in wakeful state (WA). Lead administration was discontinued after that age for allowing rehabilitation for 40 days. Then, operant behavioral assessment was done. Results revealed that the lead treated animals took significantly more time and sessions than control normal animals in attaining criterion of learning. Hence exposure to lead in early age could result in a learning disability persisting even after discontinuation of exposure.

Efficacy of pre-operative levo-phase pulmonary angiograms in detecting left atrial thrombi.

We have studied the efficacy of levo-phase pulmonary angiograms in detecting thrombosis of the left atrium or its appendage in 33 patients with rheumatic mitral stenosis who subsequently underwent open-heart surgery. Left atrial thrombi had been suspected in all these patients due to the presence of atrial fibrillation and/or history of systemic embolization. The angiographic criteria for the presence of thrombus included mobile or persistent fixed filling defects of constant size in the contrast shadow of the left atrium or its appendage, partial or complete non-visualization of the left atrial appendage, irregular outline of the left atrium or its appendage and an atrial chamber which appeared smaller than the atrial shadow. 19 patients showed one or more angiographic features of thrombosis. All the patients subsequently underwent open-heart surgery for mitral valve disease, and thrombi were found in 17 patients. The angiogram was false positive in three patients, and false negative in one patient. The angiographic diagnosis of left atrial thrombosis by levo-phase pulmonary angiography has a sensitivity of 94%, specificity of 81.3%, and predictive value of 84.2%. Non-visualization of left atrial appendage as the only feature of thrombus formation was seen in five patients, and thrombi were subsequently formed at surgery in four patients (80%). Levo-phase pulmonary angiograms are safe and reasonably accurate for preoperatively detection of left atrial thrombi, and should be performed in all the patients of mitral stenosis if left atrial thrombi are clinically suspected.