http://dkr.cdri.res.in:8080/xmlui/handle/123456789/495 2026-04-19T13:41:16Z 2026-04-19T13:41:16Z Hidau, Mahendra Kumar Singh, Yeshwant Shahi, Sudhir Mounika, Poojari Singh, Shio Kumar http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1704 2017-06-13T08:26:57Z 2015-01-01T00:00:00Z

LC-MS/MS assay for quantification of a novel Antitubercular molecule S006-830: Pharmacokinetic and plasma protein binding studies in Rats Hidau, Mahendra Kumar; Singh, Yeshwant; Shahi, Sudhir; Mounika, Poojari; Singh, Shio Kumar A highly sensitive and selective LC-MS/MS assay was developed and validated for determination of a novel antitubercular compound S006-830 in rat plasma. The analyte and internal standard (IS) were extracted from plasma by a two step liquid–liquid extraction procedure using 2% isopropanol in n-hexane. Chromatographic separation was achieved on a Phenomenex, Luna C-18 column (3µm, 100mm x 2mm i.d.) under isocratic condition [92:8 (v/v); ACN (0.1% formic acid) : ammonium acetate buffer (10 mM, pH 4)] at a flow rate of 0.450 ml/min. The quantification was performed on Q-trap 5500 LC-MS/MS coupled with ekspert ultra LC 100-XL system (AB Sciex).The detection was performed in positive electrospray mode using multiple reaction monitoring. The precursor to production ion transitions selected for quantification of S006-830 and IS were m/z 424.353/203.00 and 330.300/267.400 respectively. LC-MS/MS method was found sensitive and reproducible over a linearity range of 0.15-40 ng/ml. Recoveries of S006-830 from spiked plasma samples were consistent and found to be more than 70%. Further, the applicability of this method has been described by determining pharmacokinetic profile and plasma protein binding of S006-830 in rats. Irregular plasma-concentration time profile was observed. Oral PK profile of S006-830 at 50 mg/Kg demonstrated that mean (±SEM) T1/2 and MRT were 8.30 ± 1.30 h and 8.44 ± 0.57 h, while Cmax and AUC0-last were 1.94 ± 0.30 µg /ml and 6.25± 1.66 µg.h /ml respectively. Plasma protein binding for S006-830 was found 58.63 ± 3.4.

2015-01-01T00:00:00Z Chhonke, Yashpal S. Chandasana, Hardik Kumar, Ashok Kumar, Deepak Laxman, Tulsankar Sachin Mishra, Sunil Kr Balaramnavar, Vishal M. Srivastava, Shishir Saxena, Anil K Bhatta, Rabi S. http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1703 2017-06-13T08:09:54Z 2015-01-01T00:00:00Z

Pharmacokinetics, tissue distribution and plasma protein binding studies of rohitukine: an potent anti-hyperlipidmic agent Chhonke, Yashpal S.; Chandasana, Hardik; Kumar, Ashok; Kumar, Deepak; Laxman, Tulsankar Sachin; Mishra, Sunil Kr; Balaramnavar, Vishal M.; Srivastava, Shishir; Saxena, Anil K; Bhatta, Rabi S. Rohitukine (RH) is a chromone alkaloid considered as one of the major active components of Dysoxylum binectariferum, exhibiting diverse pharmacological activities such as anti-hyperlipidmic, anti-cancer, anti-inflammatory, immuno-modulatory, anti-leishmanial, anti ulcer and anti-fertility. There’s still a lack of information of RH, inclusive of pharmacokinetics, tissue distribution and excretion, in vivo studies in experimental animal, such as hamster and rats. In this study, a selective and sensitive bioanalytical method was developed and validated using HPLC-UV system. The assay was applied to estimate pharmacokinetics, tissue distribution and excretion of RH in hamster at 50 mg/kg oral dose. It rapidly reached in systemic circulation and distributed to various tissues, and highest concentration was observed in liver. The pharmacokinetics parameters such as clearance (CL/F) was 3.95 ± 0.9 L/h/kg, volume of distribution (Vd/F ) was 17.34 ± 11.34 L/kg and elimination half-life was 2.62 ± 1.34 hr. RH shows moderate protein binding around ~60% and found stable in gastro-intestinal fluid, a property that favors oral administration.

2015-01-01T00:00:00Z Chandasana, Hardik Yashpal Chhonke, S Bala, Veenu Prasad, Yarra Durga Sharma, Vishnu L. Bhatta, Rabi S. http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1699 2017-06-13T07:28:10Z 2014-01-01T00:00:00Z

A rapid and sensitive LC-MS/MS analysis of diapocynin in rat plasma to investigate in-vitro and in-vivo pharmacokinetics Chandasana, Hardik; Yashpal; Chhonke, S; Bala, Veenu; Prasad, Yarra Durga; Sharma, Vishnu L.; Bhatta, Rabi S. Natural products have been used traditionally for the treatment and prevention of diseases. Diapocynin is the analogue of the naturally occurring apocynin, a well-known constituent of the Picrorhiza kurroa. It has antioxidant property and also effective in neuro-inflammatory diseases. To investigate in vitro and in vivo pharmacokinetic of the diapocynin simple and sensitive method was developed and validated in rat plasma using high-performance liquid chromatography coupled with a mass spectrometer (LC-MS/MS). The developed and validated method requires low volume of the plasma (25 µL). The analytes were extracted by simple protein precipitation method using acetonitrile. Chromatography resolution was achieved by Thermo Accucore C18 (5µ, 4.6 X 150 mm) column using mobile phase of acetonitrile and ammonium acetate buffer (10 mM, pH 4.0). Present method was successfully applied for in vitro clearance (using rat liver microsomes) and in vivo oral pharmacokinetic studies in the Sprague Dawley rats.

2014-01-01T00:00:00Z Shukla, Mahendra Sharma, Abhisheak Jaiswal, Swati Lal, Jawahar http://dkr.cdri.res.in:8080/xmlui/handle/123456789/1684 2017-05-02T11:30:26Z 2016-01-01T00:00:00Z

Insights into the Pharmacokinetic Properties of Antitubercular Drugs Shukla, Mahendra; Sharma, Abhisheak; Jaiswal, Swati; Lal, Jawahar Introduction: The furiously advancing cases of multidrug-resistant tuberculosis (TB) along with the recent emergence of total drug resistant TB and TB-AIDS comorbidity prompt an increasingly solemn threat to global public health. The knowledge of pharmacokinetic properties helps in selecting an appropriate anti-TB dosage regimen for getting optimal results in patients. Areas Covered: This article provides a brief compilation of the information available regarding published pharmacokinetic data for anti-TB drugs and may act as a single window for investigators/medical practitioners in this field. The information regarding absorption, tissue distribution, elimination and pharmacokinetic interactions of the first- and second-line anti-TB drugs and candidate drugs under clinical trials is discussed. Expert opinion: Inapt pharmacokinetic properties (such as poor absorption, too short biological half-life, extensive first-pass metabolism, drug-food and drug-drug related interactions) are not pleasing for anti-TB drugs and significantly contribute to treatment failure and further resistance. The long duration, monotonous and multidrug treatment plan leads to poor patient compliance and consequently new caveats of anti-TB drug resistance are spreading into every corner of the world. Few new agents, which are in development phase, are considering the aspect of shortening duration of the treatment regimen and provide a boost in therapy that is sorely needed.

2016-01-01T00:00:00Z