Abstract
Objective: Statistically designed and Box-Behnken design (BBD) assisted reversed-phase high-performance liquid chromatography-ultraviolet (HPLC-UV) method was developed and validated for the identification of an antipsychotic medication Olanzapine and its organic impurities in pure drug along with forced degradation studies.
 Methods: The present developed method employed BBD optimized chromatographic conditions comprising of an Inertsil ODS 3V analytical column with dimension 250 mm x 4.6 mm and particle size 5µ. The isocratic mobile phase was used as a mixture of monobasic sodium phosphate buffer (0.01 M, pH 6), methanol and acetonitrile in the proportion of 40/30/30, v/v. The mobile phase flow rate and UV λmax was 1 ml/min and 260 nm, respectively. The method was optimized by Box-Behnken design using design expert software, comprising of three factors for Olanzapine for instance flow rate (A), mobile phase composition (B) and pH (C) while resolution between Olanzapine related compound A and Olanzapine related compound B (Y1) and tailing of Olanzapine (Y2) were taken as a response.
 Results: Application of BBD yielded statistically designed method with excellent quality parameters achieved in terms of linearity with the coefficient of correlation (R2>0.9999), limit of detection (LOD, 0.0023-0.16 µg/ml), the limit of quantification (LOQ, 0.007-0.39 µg/ml), accuracy (99-100%) and precision ((2%, relative standard deviation (%RSD) were evaluated as per latest available procedures.
 Conclusion: Forced degradation conditions were carried out, demonstrated that the optimized method was stable and no any interfering peaks eluting at the similar retention time of the studied compounds. The method was found to be stable, easy, rugged and robust, could be applied for the similar types of the pure drug.
Highlights
Pure drug, Olanzapine (OLZ) is a thienobenzodiazepine derivative, chemically called as 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2-3-b][1,2,3,4,5]benzodiazepine
The opted parameters in the current analysis as per Box-Behnken design (BBD) were, flow rate (A), mobile phase composition (B) and pH (C) as variables while resolution between related compound A (RC A) and related compound B (RC B) (Y1) and tailing of OLZ (Y2) were taken as response that showed slight variation in mobile phase and flow rate affected the response while pH had no influence on these variables estimated by trails according to factorial design
We have developed an innovative, simple, cost-effective, RP-HPLC method which was duly validated by statistical parameters, precision, accuracy, recovery, limit of detection, limit of quantitation and force degradation
Summary
Olanzapine (OLZ) is a thienobenzodiazepine derivative, chemically called as 2-methyl-4-(4-methyl-1-piperazinyl)-10H-thieno [2-3-b][1,2,3,4,5]benzodiazepine. Literature revealed RP-HPLC method for the determination of OLZ by Murthy AR et al [10] They had developed a gradient system using HPLC (Shimadzu class LCSeries), system controlle SCL 10VP, with LC-10AT pump with C18 (150 mm x 4.6 mm) column by using Shimadzu class VP-5.0 software. The above reported methods were either poorly sensitive with high run time or they had very narrow linear concentration ranges, so, in the present study we had developed and validated a stability-indicating method for simultaneous estimation of OLZ in API and its organic impurities by strictly implementing quality by design (QBD), as in the current scenario as per ICH guidelines and other Europe medicines agencies had strictly ordered implementation of QBD [13]. The method is highly novel since, till date there is no evidence of detection of OLZ and its organic impurities named as Olanzapine related compound A (RC A), Olanzapine related compound B (RC B) and Olanzapine related compound C (RC C) along with forced degradation studies simultaneously by single isocratic method, the entire procedure was highly efficient as it was based on QBD and strictly follows ICH guidelines USFDA specifications, so it can be used widely for simultaneous estimation of OLZ along with its organic impurities as shown in fig. 1 in API form with high purity and compatibility
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