Development of Novel RP-HPLC Method for Separation and Estimation of Critical Geometric Isomer and Other Related Impurities of Tafluprost Drug Substance and Identification of Major Degradation Compounds by Using LC-MS.

A novel, simple, sensitive and stability-indicating reverse-phase high-performance liquid chromatography (RP-HPLC) method was developed and validated for the quantitative determination of the geometric isomer (Trans) and other related substances in the active pharmaceutical ingredient (API) of Tafluprost (TFL), with their determination by an assay. A chromatographic separation of TFL and its impurities was achieved with a C18 analytical column, using gradient elution with mobile phase A consisting of a mixture of water, methanol and orthophosphoric acid (900:100:1, v/v) and mobile phase B consisting of a mixture of acetonitrile and water (900:100, v/v). The instrumental settings included a flow rate of 1.0 mL/min for related substances and 1.2 mL/min for the assay, a column temperature of 50°C and a detector wavelength of 210 nm, using a photodiode array detector. TFL was exposed to thermal, photolytic, hydrolytic and oxidative stress conditions and the stressed samples were analyzed by the proposed method. Peak homogeneity data of TFL were obtained by using a photodiode array detector in the stressed sample chromatograms, which demonstrated the specificity of the method for estimation in the presence of degradants. The developed method was validated for parameters such as precision, accuracy, linearity, limit of detection, limit of quantification, ruggedness and robustness as per ICH guidelines.

Re-examination of the assay for plasma prostanoids by solid-phase extraction, and radioimmunoassay.

A method for the routine assay of plasma thromboxane and prostacyclin metabolites, thromboxane B2 and 6 keto-prostaglandin F1 alpha (employing solid phase extraction to remove the metabolites from interfering substances) and using commercially available antisera for their radioimmunoassay has been investigated. Modifications of previously published procedures have been explored, including the use of non-explosive solvents in the extraction procedure, and inclusion of a non-cross reacting internal standard, prostaglandin D2, to estimate recovery through the extraction procedures. Both the original and modified procedures can produce high blank values, which apparently result from the solid-phase extraction. These high backgrounds are constant for a given lot of solid phase extraction cartridges and can be corrected by subtraction. The modified method is linear with volume of plasma assayed to as little as one ml, and all cross-reacting material in normal human plasma was found to co-chromatograph with authentic standards on reverse-phase high performance liquid chromatography. Values for normal adult plasmas were found to be 0.44 +/- .15 pmol/ml 6 keto PGF1 alpha (mean +/- SD) and .103 +/- .07 for thromboxane B2. The method reported provides a convenient, reproducible way to assay these important plasma prostanoids.

[Experiences on the effectivity of prostaglandin F2alpha during labor after insufficient effect of oxytocin]. / Erfahrungen über die Effektivität von Prostaglandin F2alpha unter der Geburt nach unzureichender Oxytozinwirkung.

A report is given about the efficacy of prostaglandin F2alpha for induction of labour after inefficient application of oxytocininfusion. In all cases induction of labour was indicated or labour should be supported. 80 of the 104 women with weak labour finally delivered on vaginal way. Only 9 of 24 caesarean sections were performed by reason of weak labour in spite of application of prostaglandin F2alpha. There was no influence on the state of the newborns, this was the result of postnatal judgment by Apgar-score.

PIP: Prostaglandin F-2 alpha was applied intrapartum in 104 women who (1) had indications for induction of labor (32 of them had premature rupture of the amniotic sac) and (2) had already received ineffective infusions of oxytocin. 80 women (77%) had vaginal deliveries; 24 had to have caesarean sections. Of these 24, however, only 9 were without strong obstetric indications for caesarean section (such as fetal heartbeat, fetal acidity, or intrapartum fever). 75 of the subjects were primiparae; the age range was 16-43. The prostaglandin was in a solution of 10-15 mcg/ml; the infusion rate was 5-22.5 mcg/minute. The mean time from infusion to birth was 180 minutes; mean time from 5-cm cervical dilation to birth was 114 minutes (cervical dilation was 2-3 cm at the beginning of prostaglandin application). No harmful effect on the state of the newborn was observed, as Apgar pH scores were similar to those of children born after spontaneous labor.