Determination of Pitavastatin Calcium by Analytical Spectrophotometry

Simple and rapid spectrophotometric method for the quantitative analysis of Pitavastatin calcium (PTV) in raw material and tablets pharmaceutical formulation has been described. The method is based on the formation of yellow ion-pair complex between Pitavastatin calcium and Bromocresol purple (BCP) in chloroform medium. Different parameters affecting the reaction such as: effect of solvents, stability, reagent concentration, correlation ratio, etc. were optimized. The formed complex was quantified spectrophotometrically at absorption maximum 405 nm. Linearity range was 2.20 - 35.23 µg/mL, regression analysis showed a good correlation coefficient R2 = 0.9991. The limit of detection (LOD) and limit of quantification (LOQ) were to be 0.367 µg/mL and 1.112 µg/mL respectively. The average percent recovery was found to be (100.62 – 101.14) % for Pitavastatin Calcium. This study was applied on Syrian pharmaceutical trademark: (PAVACRIUM 4 & Londalop). The method was successfully applied for the determination of Pitavastatin calcium in tablets pharmaceutical formulation. The proposed method is simple, direct, sensitive and do not require any extraction process. Thus, this method could be readily applicable for the quality control and routine analysis.

Simultaneous Determination of Telmisartan and Pitavastatin Calcium in Intestinal Perfusate by HPLC: Application to Intestinal Absorption Interaction Study

Background: Hypertension and hypercholesterolemia are two main physiological risk factors of cardiovascular disease, and commonly occur in combination. Multicompound combination therapy is rational for the treatment of concurrent hypertension and hypercholesterolemia, while telmisartan and pitavastatin calcium can be used as a potential drug combination. Objective: The aim of this paper is to study the intestinal absorption and absorption interaction of telmisartan and pitavastatin calcium. Methods: An HPLC method was developed and validated to determine telmisartan and pitavastatin calcium in intestinal perfusate simultaneously. The in situ single-pass perfusion in rats was utilized to investigate the effects of concentrations, intestinal segment (duodenum, jejunum, ileum and colon) and co-administrated drugs on absorption. Results: The effective permeability coefficient and the absorption rate constant of telmisartan were higher in the duodenum as compared to other intestinal segments. However, the intestinal absorption of pitavastatin calcium was not segmental dependent. The effective permeability coefficient and absorption rate constant have no significant difference among three concentrations of telmisartan, pitavastatin calcium individually and their combination. Conclusion: The results showed that telmisartan and pitavastatin calcium were transported passively, and telmisartan and pitavastatin calcium could be absorbed well in all intestinal segments. The intestinal absorption parameters revealed the absence of any intestinal absorption interaction when co-administered. Lay Summary: Co-administration of telmisartan and pitavastatin calcium can provide a potential therapeutic strategy for the treatment of concurrent hypertension and hypercholesterolemia. We are investigating the intestinal interaction of these two drugs in rats using the developed HPLC method and in situ single-pass perfusion technology. We will calculate some parameters after administrating two types of drugs either separately or together, which help reflect changes regarding intestinal absorption and penetration. Compared with telmisartan and pitavastatin calcium administrated separately, if parameters significantly change after co-administration, it proves the existence of the intestinal interactions. Moreover, the results might contribute to clinic drug monitoring.

HPLC method development for estimation of pitavastatin in liquid dosage form

For the determination of pitavastatin calcium nanoemulsion liquid dosage form a simple, sensitive, reliable and rapid reversed-phase high-performance liquid chromatographic (RP-HPLC) method has been developed and validated. 5 μ particle size column in isocratic mode at 25ºC temperature. The sample was injected through an injector valve with a 10 μl, sample loop. Phosphate buffer (pH 6.4): Methanol (50:50 v/v) was used as a mobile phase with a flow rate of 1 ml per min at 286 nm wavelength. A calibration graph was plotted range between 25-200 μg/ml with the correlation coefficient of 0.999 which showed linearity. Validation studies revealed the method is specific, rapid, reliable, and reproducible. The validity of the method, degradation studies were carried out using the same optimum conditions. Therefore the proposed method is reliable, rapid, precise and selective and may be used for the quantitative analysis of nanoemulsion liquid dosage form of pitavastatin calcium.

LDL subclass lipidomics in atherogenic dyslipidemia: effect of statin therapy on bioactive lipids and dense LDL

Atherogenic LDL particles are physicochemically and metabolically heterogeneous. Can bioactive lipid cargo differentiate LDL subclasses, and thus potential atherogenicity? What is the effect of statin treatment? Obese hypertriglyceridemic hypercholesterolemic males [n = 12; lipoprotein (a) <10 mg/dl] received pitavastatin calcium (4 mg/day) for 180 days in a single-phase unblinded study. The lipidomic profiles (23 lipid classes) of five LDL subclasses fractionated from baseline and post-statin plasmas were determined by LC-MS. At baseline and on statin treatment, very small dense LDL (LDL5) was preferentially enriched (up to 3-fold) in specific lysophospholipids {LPC, lysophosphatidylinositol (LPI), lysoalkylphosphatidylcholine [LPC(O)]; 9, 0.2, and 0.14 mol per mole of apoB, respectively; all P < 0.001 vs. LDL1-4}, suggesting elevated inflammatory potential per particle. In contrast, lysophosphatidylethanolamine was uniformly distributed among LDL subclasses. Statin treatment markedly reduced absolute plasma concentrations of all LDL subclasses (up to 33.5%), including LPC, LPI, and LPC(O) contents (up to −52%), consistent with reduction in cardiovascular risk. Despite such reductions, lipotoxic ceramide load per particle in LDL1-5 (1.5–3 mol per mole of apoB; 3–7 mmol per mole of PC) was either conserved or elevated. Bioactive lipids may constitute biomarkers for the cardiometabolic risk associated with specific LDL subclasses in atherogenic dyslipidemia at baseline, and with residual risk on statin therapy.

VALIDATED KINETIC SPECTROPHOTOMETRIC DETERMINATION OF PITAVASTATIN CALCIUM USING ACIDIC PERMANGANATE OXIDATION

Objective: Development and validation of a sensitive, indirect spectrophotometric kinetic method, based on oxidation-reduction reaction, using potassium permanganate, for the quantitative assay of pitavastatin calcium, a cardiovascular drug used for the treatment of hyperlipidemia. Methods: The developed spectrophotometric kinetic method is based on the ability of potassium permanganate to oxidize Pitavastatin, where, the drug solution is treated with a fixed concentration of permanganate in acidic medium, and after a specified time, the unreacted permanganate is measured at 525 nm. All variables affecting the color development have been investigated and the conditions were optimized. Different kinetic methods, including initial rate, rate constant, fixed time and fixed concentration, were applied for the determination Pitavastatin. Results: During the course of the reaction, the absorbance values, at 525 nm, related to KMnO4, decreased linearly with increasing the concentration of the drug. The reaction rate obeyed was found to be pseudo-first-order and the kinetic method used was the fixed-time method. The assay of PITA in the concentration range of 16-80 μg/ml, using the fixed time method was successfully determined with a correlation coefficient value of 0.9999. The applicability of the developed method was also demonstrated by the determination of pitavastatin in its pure form and in its pharmaceutical formulation, where, the effect of excipients has also been studied and found to have no effect. Conclusion: The developed indirect spectrophotometric kinetic method, using the fixed time method, was used for the determination of Pitavastatin in pharmaceutical tablets. This method was simple, accurate and easy to apply for routine assay and in quality control laboratories.

SPECTROPHOTOMETRIC DETERMINATION OF ATORVASTATIN CALCIUM AND PITAVASTATIN CALCIUM THROUGH ION-PAIR COMPLEX FORMATION USING ACID DYES IN PHARMACEUTICAL FORMULATIONS AND HUMAN URINE SAMPLES

Objective: The main objective was to develop simple, cost-effective, rapid and selective spectrophotometric methods for the determination of atorvastatin calcium and pitavastatin calcium in pure and pharmaceutical formulations using acid dyes like bromothymol blue, bromocresol purple and bromocresol green and also in human urine samples. Methods: The developed methods were based on the formation of ion-pair complexes between statin drugs and acid dyes after studying the optimization conditions. The association constants of the developed ion-pair complexes were evaluated using Benesi–Hildebrand equation. The methods were validated according to ICH guidelines. Results: The formed ion-pair complexes showed maximum absorbance which was measured at 637 nm for both methods A and D, 601 nm, 606 nm for methods B and E and 631 nm for both methods C and F respectively with correlation coefficients 0.999. The analytical parameters and their effects in the developed methods were investigated. The ion-pair complexes were stable up to 24 h and showed good linearity. The molar absorptivity, Sandell sensitivity, detection, and quantification limits were also calculated. The stoichiometry ratio in all the cases was 1:2 by using Job’s method of continuous variation. The recovery studies again showed good results because co-formulated substances did not interfere for the determination of ATC and PTC in the developed methods. Conclusion: The developed methods were applicable for routine quality control analysis of ATC and PTC in pure and pharmaceutical dosage forms. Good results were obtained when the developed methods were applied in healthy human urine samples.