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For the simultaneous quantification of Azelnidipine and Chlorthalidone in synthetic combination, a high performance thin layer chromatographic method was devised that is quick, accurate, selective, and exact. The mobile phase used in the chromatographic analysis was in the ratio of 5: 4.7: 0.3: 0.1 v/v/v/v, and the stationary phase utilised was silica gel 60 F254 as the precoated stationary phase on aluminium plates. A 10 x 20 cm TLC chamber with a 15-minute saturation period was utilised. Azelnidipine and chlorthalidone were found to have retardation factors (RF) of 0.43 0.03 and 0.30 0.02, respectively. At 242 nm, densitometric analysis was performed. Following the ICH Q2 (R1) standard, a validation study was conducted. The calibration plots' regression data revealed a strong linear association with R2 = 0.999 for the concentration ranges of azelnidipine and chlorthalidone, 400–1200 ng band-1 and 600–1800 ng band-1, respectively. The method's precision, accuracy, and robustness were all validated. For azelnidipine and chlorthalidone, the minimum detectable levels were determined to be 26.71 ng band-1 and 38.39 ng band-1, respectively, and the limits of quantitation were found to be 80.94 ng band-1 and 116.033 ng band-1. Azelnidipine and chlorthalidone can be estimated simultaneously for routine analysis, in drug formulations, and in biological matrices, in short, using the proven analytical approach.

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Purpose Colorectal cancer (CRC) is the fifth most common cancer in India, however, there is a paucity of systematically collected data related to its molecular epidemiology, specifically related to tumour microsatellite instability (MSI) and Lynch syndrome prevalence. Methods We prospectively recruited 207 unrelated patients who were diagnosed with CRC from whom primary tumour biopsy along with a matched blood sample was obtained. A sequential genetic testing approach for Lynch syndrome detection in colorectal cancer patients in accordance with the UK’s National Institute of Health and Care Excellence’s guideline (DG27) was utilised. Briefly, DNA from tumour biopsies were tested for MSI status followed BRAF V600E testing in samples which showed MSI-high result. Germline testing for the mismatch repair genes was carried in patients who had MSI-high and BRAF V600E negative tumours. Seventeen patients recanted their consent to participate in the study and therefore, results from 190 out of 207 patients is presented here. Results Mean age at cancer diagnosis across the cohort was 52.3 years with male to female ratio of 2:1 and 57.3% of the patients had tumours in the descending colon or rectum. MSI-high status was observed in 79 patients (42.6%) and, was inversely associated with age (OR = 0.95, 95% CI = 0.92–0.97, p = < 0.001) and cancers in distal colon and rectum (OR = 0.42, 95% CI = 0.22–0.81, p = 0.009 for distal colon; OR = 0.13, 95% CI = 0.04–0.40, p < 0.001 for rectum). Of these, 76 patients had BRAF V600E negative mutation status (96%) and of these, 48 were diagnosed with Lynch syndrome (63%; MLH1 = 38, MSH2 = 4, MSH6 = 4, PMS2 = 1, EPCAM = 1). The variants c.154del and c.306G > T in the MLH1 gene were most commonly observed across Lynch syndrome patients in our cohort. Conclusions This is the first systematic evaluation of the molecular epidemiology of CRC in India. We observe a high proportion of patients with young onset CRC coupled with high prevalence of MSI-high status and Lynch syndrome. The study provides a unique opportunity to explore development of novel Lynch syndrome detection and cancer prevention pathway in Indian healthcare settings.