Development and validation of a sensitive LC-MS/MS method for pioglitazone: application towards pharmacokinetic and tissue distribution study in rats.
Development and validation of a sensitive LC-MS/MS method for pioglitazone: application towards pharmacokinetic and tissue distribution study in rats.
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DOI：
10.1039/d1ra01126j
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发表时间：
2021-03-16
期刊：
影响因子：
3.9
通讯作者：
Krishnaveni N
中科院分区：
文献类型：
--
作者：
G KK;Thaggikuppe Krishnamurthy P;Ammu V V V RK;Vishwanath K;Narenderan ST;Babu B;Krishnaveni N
在本研究中，开发并验证了灵敏的LC-MS/MS方法，用于测定大鼠血浆和组织中的吡格列酮（PGZ）浓度。采用YMC Pro C18色谱柱（100 mm × 4.6 mm，3μ）进行色谱分离，移动的流动相由甲酸（0.1% v/v）和乙腈（5：95）组成，流速为0.7 mL min−1，进样体积为10 μL（IS：罗格列酮）。使用三重四极杆质谱法，使用以正离子化模式操作的ESI接口进行质谱检测。所开发的方法在1-500 ng mL−1的线性范围内进行了验证，检测和定量下限分别为0.5 ng mL−1和1 ng mL−1。方法的准确度日间为95.89-98.78%，日内为93.39-97.68%，精密度日间为6.09-8.12%，日内为7.55-9.87%。PGZ在血浆中的最高Cmax为495.03 ng mL−1，在骨中的最低Cmax为24.50 ± 2.71 ng mL−1。在骨中观察到的最大Tmax为5.00 ± 0.49 h，在血浆中观察到的最小Tmax为1.01 ± 0.05 h。的AUC血浆中（0-24 h和0-∞）值最高（1056.58 ± 65.78和1069.38 ± 77.50 ng h−1 mL−1），脑中最低T1/2在血浆中最高（5.62 ± 0.74 h），在肾脏中最低（2.78 ± 0.19）。该方法已成功用于测定PGZ的药代动力学和组织分布。此外，所开发的方法可用于验证除常规剂型之外的PGZ（纳米制剂）的靶器官（脂肪组织）特异性递送。研究了所开发的方法用于吡格列酮的靶向和脱靶分布，并可用于验证位点特异性递送系统。
In the present study, a sensitive LC-MS/MS method was developed and validated to measure pioglitazone (PGZ) concentrations in rat plasma and tissues. The chromatographic separation was achieved by using a YMC Pro C18 column (100 mm × 4.6 mm, 3μ) with a mobile phase consisting of formic acid (0.1% v/v) and acetonitrile (5 : 95) at a flow rate of 0.7 mL min−1 and injection volume of 10 μL (IS: rosiglitazone). Mass spectrometric detection was done using triple quadrupole mass spectrometry using the ESI interface operating in a positive ionization mode. The developed method was validated over a linearity range of 1–500 ng mL−1 with detection and a lower quantification limit of 0.5 ng mL−1 and 1 ng mL−1. The method accuracy ranged from 95.89–98.78% (inter-day) & 93.39–97.68% (intra-day) with a precision range of 6.09–8.12% for inter-day & 7.55–9.87% for intra-day, respectively. The PGZ shows the highest Cmax of 495.03 ng mL−1 in plasma and the lowest Cmax, 24.50 ± 2.71 ng mL−1 in bone. The maximum Tmax of 5.00 ± 0.49 h was observed in bone and a minimum of 1.01 ± 0.05 h in plasma. The AUC(0–24 h and 0–∞) values are highest in plasma (1056.58 ± 65.78 & 1069.38 ± 77.50 ng h−1 mL−1) and lowest in brain (166.93 ± 15.70 &167.12 ± 16.77 ng h−1 mL−1), and the T1/2 was highest in plasma (5.62 ± 0.74 h) and lowest in kidney (2.78 ± 0.19). The developed method was successfully used to measure the PGZ pharmacokinetic and tissue distribution. Further, the developed method could be utilized for validating target organ (adipose tissue) specific delivery of PGZ (nano-formulations) in addition to conventional dosage forms. The developed method was investigated for target and off-target distribution of pioglitazone and could be applied to validate the site-specific delivery systems.
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DOI：
10.1016/j.plefa.2005.04.008
发表时间：
2005-07-01
影响因子：
3
作者：
Hammarstedt, A;Andersson, CX;Smith, U
通讯作者：
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DOI：
10.1016/j.jpba.2009.12.019
发表时间：
2010-06-05
影响因子：
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影响因子：
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通讯作者：
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DOI：
10.1073/pnas.0306743102
发表时间：
2005-04-26
影响因子：
11.1
作者：
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通讯作者：
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DOI：
10.1161/atvbaha.108.179689
发表时间：
2010-05-01
影响因子：
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作者：
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