Development of the Method of Simultaneous Quantitative Determination of Loratadine and Auxuilary Substances in the Combined Syrup "Loratadin+"

Aim. The aim of the present study was to develop a method for the simultaneous determination of loratadine and auxiliary substances - methyl parahydroxybenzoate and propyl parahydroxybenzoate in the combined "Loratadine+" syrup in the presence of a bupleurum aurus grass extract.Materials and methods. Liquid chromatography separation was performed using a Shimadzu Nexera X2 LC-30AD HPLC system (Shimadzu, Japan) composed of a quaternary pump, an on-line degasser, a column temperature controller, the SIL-30AC autosampler (Shimadzu, Japan); the CTO-20AC thermostat (Shimadzu, Japan) as well as the SPD-M20A diode array detector (DAD).Results and discussion. Identification of the main component and impurities in the combined syrup was performed by determining the retention times of peaks of loratadine, methyl parahydroxybenzoate and propyl parahydroxybenzoate on the chromatogram of the test solution, obtained by quantifying them, which coincided with the retention times of the corresponding peaks on the chromatogram of the reference solution.When developing a quantitative determination method, it was found that using the gradient mode, the best separation between the compounds was observed, the separation coefficient between the peaks of methyl parahydroxybenzoate and the peaks closest to it became more than 2.5, in the case of propyl parahydroxybenzoate this index was more than 3.To confirm the correctness of the proposed method, validation studies were carried out in accordance with the requirements of SPHU. It was established that the uncertainty of sample preparation is 1.5 % for loratadine, 1.47 % for methyl parahydroxybenzoate, and 1.53 % for propyl parahydroxybenzoate, which does not exceed the acceptance criteria. The specificity of the technique was confirmed by comparing the chromatograms of the reference solution, the test solution and the chromatogram of the blank solution. Requirements for the linearity of the method were performed over the entire range of concentrations for loratadine and both excipients. The correlation coefficients were 0.9999, 0.9999 and 0.9995, respectively. The correctness of the technique was carried out according to two criteria - practical and statistical insignificance, which were determined in the course of experimental studies. The results of the assessment of intralaboratory precision showed that the obtained values of the confidence interval of the average result to the criteria of acceptability. Based on the results of the determination of robustness, it was found that for optimal chromatographic conditions, a freshly prepared reference solution can be used within 24 hours.Conclusions. A method was developed for the simultaneous quantitative determination of loratadine and auxiliary substances - methyl parahydroxybenzoate and propyl parahydroxybenzoate in the syrup of "Loratadine+". The conditions that allow to correctly determining all the components in the presence of a bupleurum aurus grass extract were determined. The correctness of the methodology is confirmed by validation studie

РАзрАботкА методИкИ кОличественнОгО определениЯ бИологИческИ активныХ ВещестВ экстрАктА володушкИ золотистоЙ В составЕ комбинированноЙ лекарственноЙ формЫ

В настоящее время все большего распространения приобретают комбинированные лекарственные средства. Комбинирование активных фармацевтических ингредиентов необходимо для повышения терапевтического эффекта или сокращения периода лечения, или предотвращения возможных осложнений. Целью работы – является разработка методики количественного определения биологически активных соединений сухого экстракта володушки золотистой в составе комбинированной лекарственной формы в виде сиропа в смеси с лоратадином. Методы. Идентификацию флавоноидов в экстракте осуществляли методом ВЭЖХ. Для определения количественного содержания веществ флавоноидного строения использовали метод абсорбционной спектрофотометрии в видимой области спектра, основанный на образовании окрашенных комплексов флавоноидов с раствором алюминия хлорида в кислой среде.Результаты исследований. В результате проведенных исследований разработана спектрофотометрическая методика количественного определения суммы флавоноидов в комбинированном сиропе с лоратадином и экстрактом володушки сухим. Методом ВЭЖХ установлены флавоноиды, содержащиеся в экстракте. Полученные окрашенные комплексы спиртовых извлечений из сиропа после реакции взаимодействия с раствором алюминия хлорида в уксуснокислой среде характеризовались наличием максимумов поглощения при длине волны 412 нм. Влияние фонового поглощения является незначимым δnoise=0,25 % max δ=0,51 %. Изученные валидационные характеристики методики, которые свидетельствуют о линейной зависимости количества суммы флавоноидов в пересчете на рутин в диапазоне концентрации экстракта володушки золотистого в сиропе от 80 % до 120 %, так как величина коэффициента корреляции (r) составляет 0,9999 ³ 0,9981; угловой коэффициент линейной зависимости (b) равен 0,9947, свободный член линейной зависимости (а) – 0,52 £ 1,60. Методика прецизионная, поскольку значение относительного доверительного интервала меньше критического значения для сходимости результатов: D % = 0,37 ≤ 2,60 и выполняется критерий незначимости систематической ошибки d = 0,01.Выводы. Методом ВЭЖХ установлено наличие в сухом экстракте надземной части володушки золотистой веществ флавоноидного строения, что стало предпосылкой к стандартизации действующего вещества в сиропе по сумме именно этих биологически активных соединений. Разработана спектрофотометрическая методика количественного определения в видимой области суммы флавоноидов в пересчете на рутин в комбинированной лекарственной форме в виде сиропа в присутствии другого действующего ингредиента лоратадин

A population-based study of inferior vena cava filters in patients with acute venous thromboembolism

BACKGROUND: Our study objective was to describe the frequency, indications, and outcomes after inferior vena cava (IVC) filter placement in a population-based sample of residents of the Worcester, Massachusetts, metropolitan area who had been diagnosed as having acute venous thromboembolism (VTE) in 1999, 2001, and 2003. METHODS: A retrospective chart review of inpatient and outpatient medical records was conducted. Recorded indication(s) for IVC filter placement was determined among a subset of cases from 3 Worcester tertiary care hospitals. Three thrombosis specialists assessed the appropriateness of IVC filter placement. RESULTS: Of 1547 greater Worcester residents with validated acute VTE and without a prior IVC filter, 203 (13.1%) had an IVC filter placed after acute VTE. Patients with an IVC filter were older, had more comorbidities, and had a higher mortality rate during 3 years of follow-up. There was unanimous agreement by panel members that the use of an IVC filter was appropriate in 51% of cases and inappropriate in 26% of cases, with no consensus in the remaining 23%. CONCLUSIONS: In this community-based study, IVC filters were frequently used in the treatment of patients with acute VTE. Placement was deemed to be appropriate in approximately 50% of the patients but was not appropriate or debatable in the remaining cases. Given the increasing use of IVC filters, prospective studies are clearly needed to better define the indications for, and efficacy of, IVC filter placement

Isolated calf deep vein thrombosis in the community setting: the Worcester Venous Thromboembolism study

The prevalence of isolated calf deep vein thrombosis (DVT) in the community setting is relatively unexplored. Confusion remains with regards to its management and contemporary natural history. The purpose of this investigation was to describe the number of cases of calf DVT in the community, use of early management strategies, and rates of venous thromboembolism (VTE) recurrence and major bleeding. The medical records of residents of the Worcester (MA) metropolitan area with ICD-9 codes consistent with potential VTE during 4 study years (1999/2001/2003/2005) were validated by trained nurses. Patient demographic/clinical characteristics, treatment practices, and outcomes were evaluated. Isolated calf DVT was diagnosed in 166 (11.1%) of 1,495 patients with lower extremity DVT. Patients with calf DVT were less likely to be discharged on anticoagulants or with an IVC filter than patients with proximal DVT (84.1 vs. 92.3%). The rates of VTE recurrence and pulmonary embolism did not differ significantly between patients with calf DVT and proximal DVT at 6 months (11.0 vs. 8.7%, 2.6 vs. 1.8%, respectively). Patients with calf DVT had higher adjusted risk of early (14-day) VTE recurrence/extension (OR 2.34, 95% CI 1.01-5.44). Patients with calf DVT had lower rates of major bleeding at 6 months compared to patients with proximal DVT (5.2 vs. 9.3%, P = 0.04). Rates of recurrent VTE and major bleeding following calf DVT in the community are much higher than in randomized clinical trials of patients with proximal or calf DVT. Further study of management strategies for isolated calf DVT is needed