CN103399101A - Method for detecting content of related substances of loratadine hydrochloride capsules - Google Patents
Method for detecting content of related substances of loratadine hydrochloride capsules Download PDFInfo
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- CN103399101A CN103399101A CN2013103709212A CN201310370921A CN103399101A CN 103399101 A CN103399101 A CN 103399101A CN 2013103709212 A CN2013103709212 A CN 2013103709212A CN 201310370921 A CN201310370921 A CN 201310370921A CN 103399101 A CN103399101 A CN 103399101A
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Abstract
The invention provides a method for detecting content of related substances of loratadine hydrochloride capsules. High performance liquid chromatography is adopted, and the chromatographic conditions are that a filling agent refers to an octadecyl silane bonded silica gel column; the mobile phase is formed by mixing acetonitrile and a 0.05mol/L phosphoric acid solution according to a volume ratio of 70:30 and regulating the pH value to 3.0 by using triethylamine; the column temperature is 40 DEG C, the detection wavelength is 250nm, and the flow velocity is 1.0mL/min. According to methodology validation test, the feasibility of the established detection method is verified, and the result proves that the detection method has the characteristics of high simplicity, rapidness and accuracy, is high in specificity and has high system adaptability and reproducibility.
Description
Technical field
The present invention relates to technical field of pharmaceuticals, and in particular to a kind of detection method of lorapadine hydrochloride capsule about content of material.Background technology
Lorapadine hydrochloride is long-acting tricyclic antidepressants antihistamine, its chemical entitled 4-（Chloro- 5,6- dihydros -11H- benzos [5,6] suberyl [1, the 2-b] alkene of pyridine -11 of 8-）- 1 piperidine carboxylate's hydrochloride, by optionally antagonism peripheral H1-receptor, can alleviate the nose or non-sniffle of seasonal allergic rhinitis, at present category non-prescribed medicine management area.It is reported that lorapadine hydrochloride oral absorption is rapid, work within 45 minutes, be the current most fast antihistamine that works, action time is up to 18~20 hours.Protein binding rate is 97%~99%.For potent, long-acting new antihistamine, to periphery H1 receptor affinities height, it is difficult to pass through blood-brain barrier, therefore without central inhibitory action.
This product is used for the relevant symptom of Reduce allergy rhinitis, and such as sneeze, runny nose and rhiocnesmus, nasal obstruction and eye are itched and burn feeling.Nose and eye symptom and sign are able to alleviate rapidly after oral drugs, also suitable for alleviating chronic urticaria, pruritus dermatopathy and the symptom and sign of other anaphylaxis dermatosis.At present, the lorapadine hydrochloride oral formulations that in the market has been developed have tablet, capsule and particle etc..
Lorapadine hydrochloride capsule has achieved good clinical therapeutic efficacy as an extensive non-prescribed medicine of prolonged application in treatment in the market.Lorapadine hydrochloride capsule is to investigate the essential parameter of this drug stabilisation about material detection, is the important evidence that science formulates drug valid period.Shown through Patents and literature search result, be showed no relevant report of the lorapadine hydrochloride capsule about material detection method.
The content of the invention
It is an object of the invention to provide a kind of simplicity, fast and accurately detection method of the lorapadine hydrochloride capsule about content of material.
Described lorapadine hydrochloride capsule is about the detection method of content of material, and using high performance liquid chromatography, chromatographic condition is：
Filler：Octadecylsilane chemically bonded silica post；
Mobile phase：Acetonitrile is mixed with 0.05mol/L phosphoric acid solutions with volume ratio 70: 30, and pH value is adjusted to 3.0 with triethylamine；
Column temperature：40℃；
Detection wavelength：250nm；
Flow velocity：1.0mL/min.
The detection method comprises the following steps：
（1）It is prepared by test solution：Precision weighs lorapadine hydrochloride capsule 200mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, and is filtered through 0.45 μm of filter membrane, takes subsequent filtrate to produce；
（2）It is prepared by contrast solution：Precision measures need testing solution 1mL, puts in 100mL measuring bottles, plus mobile phase is diluted to scale, shakes up；Extension rate relative to test solution is 100 times；
（3）Blank solution：Mobile phase；
（4）It is prepared by negative control solution：Precision weighs Loratadine reference substance 20.0mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up；
（5）Take the μ L of blank solution 20 to inject high performance liquid chromatograph, as control, judge mobile phase peak；
（6）Take the μ L of negative control solution 20 to inject high performance liquid chromatograph, record Loratadine retention time；
（7）Take the μ L of contrast solution 20 to inject high performance liquid chromatograph, measure Loratadine peak area A1；
（8）Take the μ L of test solution 20 to inject high performance liquid chromatograph, measure relevant material total peak area B2；
（9）Computational methods about content of material are：
The invention has the advantages that：
The invention provides detection method of the Loratadine capsule about content of material, with simplicity, fast and accurately feature, not only specificity is strong but also with good system suitability and reappearance.
Brief description of the drawings
Fig. 1 is Loratadine reference substance linear relationship chart.
Embodiment
The present invention is described further with reference to embodiments.
Embodiment 1
Detection method comprises the following steps：
（1）Test solution preparation method is：Precision weighs lorapadine hydrochloride capsule 200mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, and is filtered through 0.45 μm of filter membrane, takes subsequent filtrate to produce；
（2）Contrast solution preparation method is：Precision measures need testing solution 1mL, puts in 100mL measuring bottles, plus mobile phase is diluted to scale, shakes up；Extension rate relative to test solution is 100 times；
（3）Negative control solution preparation method is：Precision weighs Loratadine reference substance 20.0mg, puts in 100mL bottles, plus flows phased soln and be diluted to scale, shakes up；
（4）Blank solution：Mobile phase；
（5）Take the μ L of blank solution 20 to inject high performance liquid chromatograph, as control, judge mobile phase peak；
（6）Take the μ L of negative control solution 20 to inject high performance liquid chromatograph, record Loratadine retention time；
（7）The μ L of contrast solution 20 are taken to inject high performance liquid chromatograph, according to step（5）Loratadine retention time, measures Loratadine peak area A1；
（8）Take the μ L of need testing solution 20 to inject high performance liquid chromatograph, measure relevant material total peak area B2；
（9）Computational methods about content of material are：
Take different date of manufacture lorapadine hydrochloride capsules to keep sample to its relevant material to detect, the relevant material testing result of sample is shown in Table 1.Result of the test shows that relevant material is during 18 to 30 months investigate five batches of products within the effect phase, and change is little, and is no more than raw material detection limit.The relevant material detection limit of lorapadine hydrochloride capsule：About the summation of material peak area, the main peak area of contrast solution cannot be greater than（1.0%）.
The relevant material testing result table of the sample of table 1
Embodiment 2
Specificity：
Take each 20 μ L of need testing solution, contrast solution, negative control solution, blank solution to be injected separately into liquid chromatograph, record chromatogram.
As a result：Negative control solution is noiseless to relevant material blob detection.
Embodiment 3
System suitability：
Accurately weighed lorapadine hydrochloride capsule sample 200.0mg, equivalent to Loratadine 20mg, puts in 100mL bottles, plus flows phased soln and be diluted to scale, shakes up, and is filtered through 0.45 μm of filter membrane, is used as need testing solution.
Precision measures need testing solution lmL, puts in 100mL measuring bottles, plus mobile phase is diluted to scale, shakes up, and is used as contrast solution.
The pin of 20 μ L sample introductions of contrast solution 5 is taken, chromatogram is recorded.Theoretical cam curve is not less than 3000, and the RSD of peak area is not more than 2.0%, should be not less than 1.5 with neighbors mass peak separating degree.
Test data is shown in Table 2
The system suitability tables of data of table 2
| Number of injections | l | 2 | 3 | 4 | 5 | RSD (%) | Post is imitated | Separating degree |
| Main peak area | 91125 | 90987 | 910730 | 91084 | 90942 | 0.1 | 11889 | 5.5 |
Embodiment 4
Repeatability：
Precision weighs lorapadine hydrochloride sample 200.0mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, is used as need testing solution.
Precision measures need testing solution lmL, puts in 100mL measuring bottles, plus mobile phase is diluted to scale, shakes up, and is used as contrast solution.6 parts are prepared with method.
Precision measures the μ L sample introductions of contrast solution 20, records chromatogram, and test result is shown in Table 3, and the RSD of peak area is not more than 2.0%.
The replica test result of table 3 and relative standard deviation
| Number of times | l | 2 | 3 | 4 | 5 | 6 | Average value | RSD (%) |
| Peak area | 90942 | 9079l | 90845 | 91143 | 91093 | 91197 | 91002 | 0.2 |
| Retention time | 7.404 | 7.403 | 7.399 | 7.399 | 7.417 | 7.40l | 7.404 | 0.1 |
Embodiment 5
Intermediate precision
By another lab technician, high performance liquid chromatograph is changed, is measured by the method for embodiment 4, test data is shown in Table 4.Found out by testing result, different personnel are different, and detecting instrument testing result is basically identical, and mean relative deviation meets the requirements.
The intermediate precision degrees of data of table 4
| Number of times | l | 2 | 3 | 4 | 5 | 6 | RSD (%) |
| Peak area | 92985 | 9152l | 91214 | 91628 | 91930 | 92467 | 0.8 |
| Retention time | 7.335 | 7.319 | 7.309 | 7.314 | 7.318 | 7.320 | 0.2 |
Embodiment 6
Test limit, the measure of quantitative limit
Certain density solution is prepared, 20 μ L sample introductions are taken, chromatogram is recorded.
It is required that：Test limit:Signal to noise ratio S/N=2~3；
Quantitative limit:Signal to noise ratio S/N=10~20.
Computing formula and result：
Test limit LOD (%)=minimum detectable concentration × 100%/sample concentration；
Quantitative limit LOQ (%)=minimum quantitative concentrations × 100%/sample concentration；
The quantitative limit of table 5 and test limit
Embodiment 7
Linearly：
Precision weighs Loratadine reference substance 20.0mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, is used as linear stock solution.
Linear stock solution 1mL, 1.5mL are measured respectively in 100mL measuring bottles, scale is diluted to mobile phase, shakes up, and linear test fluid 5,6 are obtained, equivalent to the 0.2% of sample solution concentration, 0.3%.
Precision measures the linear test fluids 5 of 1mL, is respectively placed in 100mL, 20mL measuring bottles, plus mobile phase is diluted to scale, shakes up, and linear test fluid 2,3 is obtained, equivalent to the 0.002% of sample solution concentration, 0.01%.
Precision measures the linear test fluids 5 of 2mL, puts in 10mL measuring bottles, plus mobile phase is diluted to scale, shakes up, and linear test fluid 4 is obtained, equivalent to the 0.04% of sample solution concentration.
Quantitative limit solution is linear test fluid 1.Take above-mentioned linear test fluid sample introduction respectively, each concentration sample introduction 2 times records chromatogram, test result is shown in Table 6, Loratadine reference substance linear relationship such as Fig. 1.
The linear test data of table 6
Embodiment 8
The degree of accuracy：
The degree of accuracy is tested using standard addition method
Sample：Lorapadine hydrochloride capsule lot number 110101, Loratadine content 9.823%
Compare stock solution：Precision claims Loratadine reference substance 20.0mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, and is used as control stock solution.
Test fluid 1：Accurately weigh lorapadine hydrochloride capsule sample 0.2g, with flowing phased soln and being diluted to 100mL, precision measures subsequent filtrate 0.3mL in 100nL volumetric flasks respectively, then essence takes control stock solution 0.5mL in 100mL volumetric flasks, scale is diluted to mobile phase, 3 parts are prepared with method.
Test fluid 2：Accurately weigh lorapadine hydrochloride capsule sample 0.2g, with flowing phased soln and being diluted to 100mL, precision measures subsequent filtrate 0.5mL in 100nL volumetric flasks respectively, then essence takes control stock solution 0.5ml in 100mL volumetric flasks, scale is diluted to mobile phase, 3 parts are prepared with method.
Test fluid 3：Accurately weigh lorapadine hydrochloride capsule sample 0.2g, with flowing phased soln and being diluted to 100mL, precision measures subsequent filtrate 0.7mL in 100nL volumetric flasks respectively, then essence takes control stock solution 0.5ml in 100mL volumetric flasks, scale is diluted to mobile phase, 3 parts are prepared with method.
Control stock solution, blank, test fluid sample introduction are taken respectively, record chromatogram.The rate of recovery should be in the range of 95.0%~105.0%.
The degree of accuracy test result of table 7
Embodiment 9
Stability：
Condition determination is constant, takes test liquid to place different time sample introduction, records chromatogram, test result is shown in Table 8.By lorapadine hydrochloride it can be seen from the data of stability test in 8 hours peak area RSD%≤2.0%, impurity peaks without exception occur,
Show that lorapadine hydrochloride stability of solution is preferable.
The stability test result of table 8
Claims (2)
1. a kind of lorapadine hydrochloride capsule is about the detection method of content of material, it is characterised in that use high performance liquid chromatography, its chromatographic condition is：
Filler：Octadecylsilane chemically bonded silica post；
Mobile phase：Acetonitrile is mixed with 0.05mol/L phosphoric acid solutions with volume ratio 70: 30, and pH value is adjusted to 3.0 with triethylamine；
Column temperature：40℃；
Detection wavelength：250nm；
Flow velocity：1.0mL/min.
2. lorapadine hydrochloride capsule according to claim 1 is about the detection method of content of material, it is characterised in that comprise the following steps：
（1）It is prepared by test solution：Precision weighs lorapadine hydrochloride capsule 200mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up, and is filtered through 0.45 μm of filter membrane, takes subsequent filtrate to produce；
（2）It is prepared by contrast solution：Precision measures need testing solution 1mL, puts in 100mL measuring bottles, plus mobile phase is diluted to scale, shakes up；
（3）Blank solution：Mobile phase；
（4）It is prepared by negative control solution：Precision weighs Loratadine reference substance 20.0mg, puts in 100mL measuring bottles, plus flows phased soln and be diluted to scale, shakes up；
（5）Take the μ L of blank solution 20 to inject high performance liquid chromatograph, as control, judge mobile phase peak；
（6）Take the μ L of negative control solution 20 to inject high performance liquid chromatograph, record Loratadine retention time；
（7）Take the μ L of contrast solution 20 to inject high performance liquid chromatograph, measure Loratadine peak area A1；
（8）Take the μ L of test solution 20 to inject high performance liquid chromatograph, measure relevant material total peak area B2；
（9）Computational methods about content of material are：
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114624358A (en) * | 2022-03-11 | 2022-06-14 | 哈尔滨圣泰生物制药有限公司 | Quality detection method of desloratadine oral liquid |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502515A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Hydrochloride loratadine enteric-coated formulation composition and method for preparing the same |
| JP2012031138A (en) * | 2010-07-08 | 2012-02-16 | Sawai Pharmaceutical Co Ltd | Method of manufacturing loratadine-containing intraoral disintegrable tablet |
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2013
- 2013-08-22 CN CN2013103709212A patent/CN103399101A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101502515A (en) * | 2008-09-04 | 2009-08-12 | 山东淄博新达制药有限公司 | Hydrochloride loratadine enteric-coated formulation composition and method for preparing the same |
| JP2012031138A (en) * | 2010-07-08 | 2012-02-16 | Sawai Pharmaceutical Co Ltd | Method of manufacturing loratadine-containing intraoral disintegrable tablet |
Non-Patent Citations (2)
| Title |
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| 尤兆珍等: "RPOHPLC测定氯雷他定颗粒剂中氯雷他定的含量", 《现代医学》 * |
| 赵亚萍: "HPLC法检查氯雷他定及其制剂的有关物质", 《中国药品标准》 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN114624358A (en) * | 2022-03-11 | 2022-06-14 | 哈尔滨圣泰生物制药有限公司 | Quality detection method of desloratadine oral liquid |
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Application publication date: 20131120 |