کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1212945 1494047 2015 9 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Development and validation of an improved HPLC-MS/MS method for comparative pharmacokinetics of penehyclidine hydrochloride following a single intravenous or intramuscular injection
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آنالیزی یا شیمی تجزیه
پیش نمایش صفحه اول مقاله
Development and validation of an improved HPLC-MS/MS method for comparative pharmacokinetics of penehyclidine hydrochloride following a single intravenous or intramuscular injection
چکیده انگلیسی


• Developing an improved HPLC-MS/MS method to determine PHC in human plasma/urine.
• PHC was well tolerate via i.v. or i.m. administration routes.
• PHC was nearly absorbed completely via the i.m. administration route.
• The two administration routes of PHC are interchangeable in clinical practice.

Penehyclidine hydrochloride (PHC) is an anticholinergic drug with both antimuscarinic and antinicotinic activity. In order to compare the pharmacokinetics of two administration routes (intravenous injection (i.v.) and intramuscular injection (i.m.)) of PHC, an improved High Performance Liquid Chromatography Tandem Mass Spectrometry (HPLC-MS/MS) bioanalytical method was developed for the quantification of PHC in plasma and urine using verapamil as the internal standard (I.S.). Chromatography was performed using a Thermo Hypersil GOLD column (30 mm × 2.1 mm, 3 μm), with a gradient elution of 1‰ formic acid–10 mmol/L ammonium acetate and acetonitrile at 0.3 mL/min. Detection and quantitation were performed by electrospray ionization (ESI) and multiple reaction monitoring (MRM) in the positive ion mode. The most intense [M + H]+ MRM transition of PHC at m/z 316.2 → 128.3 was used for PHC quantitation, and the transition at m/z 454.6 → 303.2 was used to monitor I.S. The lower limit of quantification (LLOQ) was 0.05 ng/mL. The intraday precision was <6.71% and the interday precision was <11.69%. The pharmacokinetic parameters of i.v. and i.m. administration routes were as follows (i.v. vs i.m.): t1/2 15.73 vs 17.24 h, Tmax 0.06 vs 0.26 h, AUC0–t 69.35 vs 67.90 h ng/mL, AUC0–inf 78.24 vs 79.67 h ng/mL, Cmax 37.5 vs 9.1 ng/mL, Ae0–24 h 22.7 vs 25.21 μg. There were no significant differences between parameters t1/2 and AUC (P > 0.05), but significant differences were observed in Cmax, Tmax and Ae0–24h between the two administration routes (P < 0.05). The mean absolute bioavailability of the i.m. administration route was 98.4% (95% confidence interval, 93.4–103.6%). Safety results showed that PHC appeared to be well tolerated in both i.v. and i.m. administration routes and pharmacokinetic results showed that PHC was nearly completely absorbed via i.m. administration route.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Journal of Chromatography B - Volume 1004, 1 November 2015, Pages 37–45
نویسندگان
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