Detection method of quality cold relief capsule

[0048] Example:

[0049] A detection method for Ganyu capsules. According to parts by weight, the capsules are prepared into 1000 capsules with 250g isatidis, 150g honeysuckle, 10g artificial bezoar, 250g paracetamol, 100g amantadine hydrochloride and 3.3g starch Agent; It is characterized in that, this detection method comprises the following steps:

[0050] 1. Properties: This product is a capsule, and the content is a yellow-brown powder; it tastes bitter;

[0051] 2. Identification:

[0052] (1) Take 4g of the content of this product, add 20ml of petroleum ether (60-90°C), ultrasonicate for 20 minutes, discard the petroleum ether, add 30ml of ethyl acetate to the residue, ultrasonicate for 30 minutes, filter, and evaporate the filtrate to dryness. Add 2ml of ethyl acetate to the residue to dissolve it, and use it as the test solution; take another chlorogenic acid reference substance, add methanol to make a solution containing 0.5mg per 1ml, and use it as the reference solution; test according to thin-layer chromatography, absorb the test substance 10 μl of the product solution and 2 μl of the reference solution were respectively spotted on the same polyamide film, and the upper layer solution of toluene-ethyl acetate-formic acid-water (2:30:2:2:4) was used as the developer, developed, taken out, Dry it, and inspect it under an ultraviolet lamp (365nm); in the chromatogram of the test product, on the position corresponding to the chromatogram of the reference product, there are fluorescent spots of the same color;

[0053] (2) Take 1.2g of the content of this product, add 20ml of chloroform, ultrasonicate for 30 minutes, filter, evaporate the filtrate to dryness, add 1ml of ethanol to the residue to dissolve, and use it as the test solution; take cholic acid and hyodeoxycholic acid as controls Add ethanol to make a mixed solution containing 2mg per 1ml, as the reference substance solution; according to thin-layer chromatography; test, absorb 5 μl of the test solution and 2 μl of the reference solution, and place them on the same polyamide film respectively, Isooctane-ethyl acetate-glacial acetic acid (15:7:5) (v/v) is used as the developing agent, develop, take out, dry in the air, spray with 10% sulfuric acid ethanol solution, heat at 105°C until the spots are clearly colored , placed under an ultraviolet lamp (365nm) to inspect; in the chromatogram of the test product, on the position corresponding to the chromatogram of the reference substance, there are fluorescent spots of the same color;

[0054] (3) Take 0.4g of the content of this product, add 5ml of chloroform, shake, filter, and the filtrate is used as the test solution; take another amantadine hydrochloride reference substance, add chloroform to make a solution containing 5mg per 1ml, as a control product solution; according to the thin-layer chromatography test, draw 5 μ l of each of the above two solutions, and spot them on the same silica gel GF254 thin-layer plate respectively, and use chloroform-methanol-acetone-concentrated ammonia test solution (9:1:1:0.012) ( v/v) is a developing agent, put in a developing cylinder saturated with ammonia vapor, develop, take out, dry, spray with improved bismuth potassium iodide test solution, and inspect under an ultraviolet lamp (254nm); in the chromatography of the test product, At the position corresponding to the chromatogram of the reference substance, spots of the same color are displayed;

[0055] 3. Inspection: heavy metals shall not exceed 20 parts per million; other provisions shall comply with the relevant regulations under capsules;

[0056] 4. Content determination:

[0057] Acetaminophen and amantadine hydrochloride were determined by high performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD):

[0058] Chromatographic conditions: octadecylsilane bonded silica gel as filler; 1.0% ammonium acetate-methanol solution of 75:25 as mobile phase; pH of 1.0% ammonium acetate=3.6; drift tube temperature of evaporative light scattering detector at 105°C, the atomizing gas is N 2 , flow rate 2.85L/min, injection volume 20μl, detection wavelength 249nm.

[0059] Preparation of the reference solution: Accurately weigh the appropriate amount of the amantadine hydrochloride reference substance and the paracetamol reference substance that have been dried at 105°C for 3 hours, add methanol to dissolve and dilute to make each 1ml contain amantadine hydrochloride 0.2mg and acetaminophen hydrochloride respectively. The reference substance solution of paracetamol 0.5mg;

[0060] Preparation of the test solution: take the content of the product under the difference in loading, mix well, accurately weigh an appropriate amount of fine powder (approximately equivalent to 50 mg of amantadine hydrochloride), put it in a 50ml measuring bottle, add an appropriate amount of methanol, and ultrasonically Process (power 250W, frequency 25kHz) for 20 minutes, let cool, add methanol to dilute to the mark, shake well, filter, accurately measure 5ml of the filtrate, put it in a 25ml measuring bottle, add water to dilute to the mark, shake well, and you get it.

[0061] Determination method: Precisely draw 20 μl each of the reference substance solution and the test solution, inject it into the liquid chromatograph, measure it, and get it;

[0062] Each capsule of this product contains acetaminophen (C 8 h 9 NO 2 ) should be 90.0% to 110.0% of the labeled amount; each capsule contains amantadine hydrochloride (C 10 h 18 ClN) should be 85.0% to 115.0% of the labeled amount.

[0063] 5. Determination of dissolution curve:

[0064] Take this product, according to the dissolution rate and release rate determination method, use pH 1.2, pH 6.8, pH 4.0, and water 900ml as the dissolution medium respectively, and the speed is 50 rpm, operate according to the law, and take 15ml of the dissolution solution according to the time point , discard at least 10ml of the primary filtrate, replenish the dissolution medium in time, and take the subsequent filtrate as the test solution; according to the chromatographic conditions under the content determination item, accurately measure 20 μl of the reference solution and the test solution, and inject them into the liquid chromatograph , determined. Take another appropriate amount of amantadine hydrochloride reference substance and paracetamol reference substance that have been dried at 105°C for 3 hours, add dissolution medium to dissolve and dilute to make each 1ml contain amantadine hydrochloride 0.11mg and paracetamol 0.28mg respectively of the reference solution. Calculate the dissolution amount of each tablet based on the peak area by the external standard method, and each tablet should contain 75% of the labeled amount of amantadine hydrochloride; each tablet should contain 80% of the labeled amount of acetaminophen, which should meet the requirements.

[0065] After the analytical method was confirmed, four dissolution media (pH1.2; pH4.0; pH6.8; water) were used to determine the dissolution curves of multiple batches of samples:

[0066]Through the dissolution curve measurement of many batches of Ganyu Capsules, the similarity factor (f 2 ), investigate the intra-batch and batch-to-batch differences of samples; and compare the similarity with the dissolution curves of acetaminophen and amantadine hydrochloride single preparations published in the Japanese Orange Book, and the result is f 250 is similar.