ApplicationNews

No.X258

X-ray Analysis

High-Speed X-Ray Diffraction Analysis of Medicine Using OneSight Wide-Range High-Speed Detector

LAAN-A-XR-E032

Instrument XRD-7000

X-Ray Target Cu

Tube Voltage, Tube Current 30 kV, 40 mA

Monochromatization Ni filter

Measurement Range 2θ: 10 to 50 degrees

Scan Speed 43 degrees/minute

Detector OneSight wide-range high-speed detector

Measurement Mode Step-scan (Standard mode)

n OneSight Wide-Range High-Speed DetectorThe OneSight wide-range high-speed detector consists of a semiconductor array with more than 1000 channels. Compared with the conventional scintillation detector, higher-speed measurement is achieved due to its sensitivity, which is more than twenty times that of the scintillation type. In qualitative analysis, the scan mode can be selected from among the High Resolution, Standard, and Fast modes, in addition to the One-Shot mode in which the goniometer is fixed in place and the OneSight detector acquires a wide-angle exposure, thereby permitting high-speed, high-resolution measurement for a wide variety of samples. Here, we introduce examples of a high-speed X-ray diffraction analysis of pharmaceutical products.

n Polymorphism Analysis of MedicineAmong pharmaceuticals and organic substances, there are many cases of crystal polymorphism in which the crystal system of the substances may differ even if the chemical formula is the same. Crystal polymorphs display different characteristics, such as efficacy and solubility in the body, etc., and depending on the situation, this may lead to patent infringement. Therefore, measurement of pharmaceutical products using an X-ray diffraction instrument is important from the standpoint of quality management.Here, we conducted measurements of ranitidine having two polymorphic forms (Form 1, Form 2) and a mixture of two crystalline polymorphs using the OneSight wide-range high-speed detector.

Table 1 Analytical Conditions

Fig. 1 XRD-7000 Equipped with OneSight

Form 1

Form 2

2000

0

4000

2000

4000

I (C

ount

s)I (

Cou

nts)

10 15 20 25 30 35 40 45 50θ - 2θ (Degrees)

Fig. 2 Diffraction Patterns of Form 1 and Form 2

n Results of Polymorphism AnalysisThe diffraction patterns of Form 1 and Form 2 pure substances are shown in Fig. 2. Such a comparison of crystal polymorphs clearly illustrates the differences in diffraction peak positions even among substances having the same composition. In addition, Fig. 3 shows a comparison of the diffraction patterns (enlarged region from 10 degrees to 28 degrees) of a mixture of Form 1 and Form 2 and of an overlay display of the patterns of Form 1 and Form 2, respectively. Peaks of both Form 1 and Form 2 were observed in the mixture.Furthermore, we also conducted this measurement using the conventional scintillation detector, and compared the measurement speeds.

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No.

For Research Use Only. Not for use in diagnostic procedures.The content of this publication shall not be reproduced, altered or sold for any commercial purpose without the written approval of Shimadzu. The information contained herein is provided to you "as is" without warranty of any kind including without limitation warranties as to its accuracy or completeness. Shimadzu does not assume any responsibility or liability for any damage, whether direct or indirect, relating to the use of this publication. This publication is based upon the information available to Shimadzu on or before the date of publication, and subject to change without notice.

© Shimadzu Corporation, 2015www.shimadzu.com/an/

X258

First Edition: Jan. 2015

Mode Step-Scan (Standard mode) One-Shot

Instrument XRD-7000

X-Ray Target CuTube Voltage, Tube Current 30 kV, 40 mA

Monochromatization Ni filter

Measurement Range 2θ: 15 to 25 degrees

Integration Time 55 seconds 10 seconds

Detector OneSight wide-range high-speed detector

2|

Form 1 Form 2

Mixture

2|1

|1|

2|

1|1|

1|

1|

2|

1|

2|

2|2|

2|1|

2|

2|1

|1| 2

|

1|

1|

2|

2|

2|

1| 2

|

2|

1|

1|

2|

2|I (

Cou

nts)

I (C

ount

s)

0

2000

4000

6000

2000

4000

6000

28262420 221816141210θ - 2θ (Degrees)

I (a.

u.)

10 15 20 25 30 35 40 45 50θ - 2θ (Degrees)

OneSight High-Speed Detector (43 degrees/minute)Scintillation Detector (2 degrees/minute)

Fig. 3 Diffraction Pattern of a Mixture of Form 1 and Form 2 (above) and Overlay Pattern of Form 1 and Form 2 (below)

Using a convent iona l sc int i l la t ion detector, th i s measurement took twenty minutes, while the same measurement was completed within just a few minutes using the OneSight wide-range high-speed detector. Fig. 4 shows the overlaid diffraction patterns of Form 1 obtained using the OneSight high-speed detector (43 degrees/min) and the scintillation detector (2 degrees/min), respectively.The OneSight detector incorporates a high-speed (Fast) mode for faster measurement, and a high-resolution mode for precise analysis of each peak, and measurement can be conducted while switching back and forth between these modes.

Fig. 4 Diffraction Pattern by OneSight High-Speed Detector and Conventional Scintillation Detector

n High-Speed X-ray Diffraction Analysis of Medicine Using One-Shot Mode

Using the One-Shot analysis mode, in which the detector is fixed on the target peak position using a wide acquisition angle, it is possible to conduct quick, high-resolution measurement over a fixed range of angles. Here, we compared measurement of Drug A using the step-scan and One-Shot measurement modes.

Table 2 Analytical Conditions

Step-Scan (Standard mode) Measurement Time: 55 seconds

10 15 20 25 30 35 405θ - 2θ (Degrees)

I (C

ount

s)

0

5000

10000

20000

15000

I (C

ount

s)

0

5000

10000

20000

15000

15 20 25θ - 2θ (Degrees)

One-Shot Measurement Time: 10 seconds

Fig. 5 Measurement Time Comparison Using One-Shot Mode and Step-Scan Mode

When conducting verification measurement of a particular peak, measurement can be conducted quicker using the One-Shot mode than with the step-scan mode because scanning by the goniometer is obviated in the One-Shot mode.