Degradation Study on Sulfasalazine and a Validated HPLC-UV Method for its Stability Testing

Sulfasalazine (SSZ) was subjected to degradation under the conditions of hydrolysis (acid, alkali, and water), oxidation (30% H₂O₂), dry heat, and photolysis (UV-VIS light) in accordance with the ICH guidelines. An RP-HPLC method was developed to study the degradation behavior. No degradation was noted under any condition except alkaline hydrolysis where SSZ was degraded to a single minor product. SSZ was optimally resolved from this product on an XTerra^® RP18 column with a mobile phase composed of methanol and an ammonium acetate buffer (10 mM, pH 7.0) (48:52, v/v) delivered at a rate of 0.8 mL/min in an isocratic mode. The method was validated and found to be linear (r²=0.99945), precise (%RSD <2), robust, and accurate (94–102%) in the concentration range of 0.5–50 μg/mL of SSZ. The PDA analysis of the degraded sample revealed the SSZ peak purity to be 998.99 and the drug peak eluted with a resolution factor of >2 from the nearest resolving peak, indicating the method to be selectively stability-indicating for the drug analysis. The method was applied successfully for the stability testing of the commercially available SSZ tablets that were under varied ICH-prescribed conditions. An explanation for the unusual stability of the drug when exposed to acidic hydrolysis, despite the presence of the sulfonamide linkage, is also discussed.     

Effects of sulfasalazine on biopsy mucosal pathologies and histological grading of patients with active ulcerative colitis

AIM: To investigate the mechanisms of sulfasalazine (SASP) in the treatment of ulcerative colitis (UC). METHODS: Changes of pathological signs and histological grading of 106 patients with active UC were observed before and after the treatment with SASP, 1 g, thrice daily for 6 wk. RESULTS: The effect of SASP on the vasculitis in lamina propria was 48.2% and 17.4% in the mild active UC (P<0.001) and 68% and 26.7% in the moderate active UC (P<0.001) before and after treatment. Fibroid necrosis of vessel wall was found in one case of mild UC and two cases of moderate UC before treatment and was not found after treatment. No thrombosis was found in mild UC before and after treatment, while thrombosis was found in one case of moderate UC before treatment. The effect on mucosal glandular abnormality was 30.4% and 13.0% in mild UC (P<0.05), and 42% and 40% in moderate UC (P>0.05) before and after treatment. The rate of eosinophil infiltration was 98.2% and 80.4% in mild UC (P<0.01), and 100% and 91.1% in moderate UC (P<0.05) before and after treatment. The effect on crypt abscess was 21.4% and 4.4% in mild UC (P<0.05), and 48% and 13.3% in moderate UC (P<0.001) before and after treatment. The effect on mucosal pathohistological grading was 2.00+/-0.84 and 0.91+/-0.46 in mild UC (P<0.001), and 2.49+/-0.84 and 1.31+/-0.75 in moderate UC (P<0.001) before and after treatment. CONCLUSION: SASP can improve small vessel lesions and crypt abscesses and reduce neutrophilic and eosinophilic leukocyte infiltration in inflammatory mucosa of UC.     

玉屏风颗粒联合柳氮磺吡啶治疗慢性结肠炎的效果

目的：探讨玉屏风颗粒联合柳氮磺吡啶治疗慢性结肠炎的临床效果。方法选取2013年4月~2014年4月本院诊治的120例慢性结肠炎患者作为研究对象,随机分为两组,各60例。对照组采用柳氮磺吡啶治疗,实验组在对照组的基础上采用玉屏风颗粒治疗,比较两组的治疗效果。结果实验组的总有效率为91.7%,显著高于对照组的85.0%,差异有统计学意义（P<0.01）。实验组的满意率为91.7%,显著高于对照组的65.0%,差异有统计学意义（P<0.05）。实验组的腹痛、腹泻、里急后重、黏液脓血便及结肠镜下黏膜病变评分显著低于对照组,差异有统计学意义（P<0.05）。实验组的大便次数、发作次数显著低于对照组,差异有统计学意义（P<0.05）。结论玉屏风颗粒联合柳氮磺吡啶治疗慢性结肠炎效果显著,能够改善患者的临床症状、体征以及结肠镜下黏膜病变,值得临床推广应用。     

白头翁丸治疗慢性溃疡性结肠炎45例

目的:观察白头翁丸治疗慢性溃疡性结肠炎的临床疗效。方法:选取慢性溃疡性结肠炎患者89例,随机分为治疗组45例和对照组44例。治疗组给予白头翁丸治疗,对照组给予柳氮磺砒啶片治疗。结果:治疗组有效率为88.9%,对照组有效率为72.7%,治疗组优于对照组(P0.05)。结论:白头翁丸治疗慢性溃疡性结肠炎临床疗效显著。     

葛根芩连五炭汤联合柳氮磺吡啶治疗活动期溃疡性结肠炎临床研究

目的探讨葛根芩连五炭汤联合柳氮磺吡啶治疗活动期溃疡性结肠炎的临床效果。方法将80例活动期溃疡性结肠炎患者随机分为两组,各40例。两组患者均给予口服柳氮磺砒啶治疗,观察组在上述治疗基础上加用葛根芩连五炭汤口服,共治疗4个疗程。对比两组临床治疗效果。结果观察组患者腹痛、便血和里急后重消失时间均短于对照组(P<0.01);观察组治疗总有效率为95.00%,高于对照组的77.50%(P<0.05)。结论葛根芩连五炭汤联合柳氮磺吡啶治疗活动期溃疡性结肠炎效果显著,有助于缩短症状改善时间,值得临床推广应用。     

低剂量柳氮磺吡啶联合金双歧治疗溃疡性结肠炎的临床评价

目的：评价低剂量柳氮磺吡啶（SASP）联合金双歧治疗溃疡性结肠炎的疗效和安全性。方法：低剂量SASP（1g/次,3次／d）联合金双歧治疗61例轻中型溃疡性结肠炎患者。结果：55例患者完成了整个疗程,其临床、结肠镜和病理组织学缓解率分别为72．7％,21．8％和16．4％。61例溃疡性结肠炎患者临床显效率为63．9％,总有效率为82．0％。共有10例（16．4％）发生了1次及以上的不良反应。结论：低剂量SASP联合金双歧治疗轻中型溃疡性结肠炎的近期疗效和安全性较好,尤以临床症状改善显著。     

The effects of sulfasalazine treatment on enthesal abnormalities of inflammatory rheumatic diseases

The aim of this study was to evaluate the effects of a 1-year course of sulfasalazine monotherapy on enthesal abnormalities of inflammatory rheumatic diseases (IRDs) using ultrasonography. Thirty-six patients with IRD including 20 patients with rheumatoid arthritis (RA) and 16 patients with ankylosing spondylitis (AS) (22 women, 14 men, mean ages 43.3 ± 8.8 years), and 18 healthy controls (10 women, 8 men, mean ages 42.5 ± 9.9 years) matched by age and body mass index were enrolled in this study. For the evaluation of enthesal structures, all patients and controls underwent ultrasonographic (USG) examinations of five enthesal sites of both lower limbs using high-resolution and Doppler USG. An ultrasonographic score of lower limb enthesitis was calculated using Glasgow ultrasound enthesitis scoring system (GUESS). Clinical and laboratory activities of IRD patients were also evaluated. Patient group was made to undergo 2 g/day sulfasalazine monotherapy for 1 year. All evaluations were made at the beginning of the treatment and repeated after 1 year follow-up. Results showed that the frequency of enthesal abnormalities of the IRD group was significantly higher than controls. On USG examination, 301/1,296 (23.2%) enthesal structures were abnormal in IRD patients, and 19/648 (2.93%) structures were abnormal in controls. Mean GUESS score of the IRD group (6.40 ± 2.41) was also significantly higher than controls (1.79 ± 1.60) (p < 0.001). Although there was a significant improvement in clinical and laboratory activity parameters of the IRD patients, significant decrease was not observed in enthesal abnormalities (295/1,296 enthesal structures—22.7%) and mean GUESS score (6.20 ± 2.38) after 1 year sulfasalazine trial. Additionally, there was no significant improvement in enthesal abnormalities and mean GUESS scores of AS and RA subgroups separately. Sulfasalazine treatment was not found effective on enthesal abnormalities of IRD patients. Further studies with larger groups including other IRDs are required to validate our results.     

Sulfasalazine-induced pericarditis in a patient with ulcerative colitis without recurrence when switching to mesalazine

Introduction Pericarditis is rarely reported in inflammatory bowel disease. Besides its common causes, pericarditis could be related to ulcerative colitis flare or to 5-aminosalicylic acid (5-ASA) treatment. Case report We report the case of a patient in whom fever, weight loss and pericarditis developed after 16 years of treatment with sulfasalazine for ulcerative colitis, after increasing the daily dosage from 1 to 3 g. Discussion The patient recovered after treatment discontinuation and did not exhibit any recurrence of pericarditis when treatment with mesalazine was introduced. Conclusion In conclusion, if pericarditis occurs in ulcerative colitis patients treated with 5-ASA compounds, the treatment should be considered as a possible cause, even after an increase of the dosage. In this case, discontinuation of the treatment and cautious switch to another 5-ASA compound should be tested.     

正清风痛宁联合甲氨蝶呤对类风湿性关节炎的治疗价值

目的观察正清风痛宁联合甲氨堞呤治疗类风湿性关节炎的疗效。方法将80例类风湿性关节炎患者,随机分为治疗组42例扣对照组38例。对照组予甲氨蝶呤联合柳氮磺吡啶,以及对症治疗;治疗组以正清风痛宁联合甲氨蝶呤治疗,疗程均为半年。结果坚持治疗半年后,两组病人的关节疼痛、肿胀、压痛,关节活动度、晨僵时间,均有明显的改善与好转,但治疗组总有效率95．2％（40／42）,疗效明显优于对照组的82．5％（33／38）;（P〈0．05）,且副作用轻微。结论正清风痛宁联合甲氨蝶呤治疗类风湿性关节炎,效果显著,且安全性与依从性好。     

导数光谱法测定生物样品中柳氮磺吡啶及其代谢产物

目的建立一种同时测定生物样品中柳氮磺吡啶,5-氨基水杨酸和磺胺吡啶含量的方法。方法选用蛋白沉淀法,以丙酮或乙醇作为沉淀剂对生物样品进行前处理,并采用一级导数光谱法消除三者紫外吸收的干扰。结果实验的各项指标均达到国家规定的生物药物分析标准,生物样品萃取回收率均>79.1%,方法回收率在70.80%~115.6%,日内日间精密度(n=5)均<10%。结论该方法简便、快速、可靠,适用于上述3种药物的生物样品分析。